The blood–brain barrier protects neural tissue by tightly regulating which substances can leave the bloodstream and enter the brain. While this defense is essential for preventing toxins and pathogens from reaching delicate neurons, it also blocks many potentially valuable drugs, including proteins, nucleic acids and some small-molecule therapies. As a result, treatments for conditions such as Alzheimer’s disease, Parkinson’s disease, brain tumors, epilepsy and stroke may require high systemic doses, invasive administration or delivery methods that remain difficult to scale.

Intranasal administration has attracted intense interest because the upper nasal cavity provides anatomical connections to the brain through the olfactory and trigeminal nerve pathways. Drugs deposited near the olfactory epithelium may move along or around these pathways, potentially reaching regions of the central nervous system without first circulating throughout the body. This concept, often described as nose-to-brain delivery, could reduce systemic exposure and allow therapeutics to act more directly at their intended site. Yet the nasal route is not automatically efficient: mucus, enzymatic degradation, rapid clearance and limited absorptive surface area can all reduce the amount of medicine that reaches neural tissue.

The review focuses on autonomous systems engineered to respond to their biological surroundings rather than simply releasing a drug at a predetermined rate. These platforms may use nanoscale or microscale carriers that alter their behavior when they encounter changes in pH, temperature, enzymes, ionic strength or other features of the nasal environment. Some are designed to adhere temporarily to the nasal mucosa, extending residence time despite the constant movement of mucus toward the throat. Others can change their structure, swell, dissolve or release their cargo in response to local signals, creating a more controlled delivery profile.

Nanoparticles are central to many of these approaches. Lipid-based particles, polymeric nanoparticles, nanogels and other engineered carriers can protect fragile payloads from degradation and improve their interaction with nasal tissues. Surface chemistry is particularly important. By adding mucoadhesive components, researchers can help particles remain in contact with the epithelium; by incorporating mucus-penetrating coatings, they may enable carriers to move through the mucus layer and approach the underlying cells. The challenge is to balance these opposing properties, because excessive adhesion can trap a carrier in mucus while insufficient adhesion can lead to rapid removal.

Autonomous delivery systems may also be engineered to cross cellular barriers or release medicines only after reaching a particular biological compartment. For example, a carrier could protect a protein or messenger RNA during administration, promote uptake by nasal epithelial cells and then release its cargo inside the cell. Other designs aim to transport drugs along neuronal pathways or encourage passage through tissues surrounding the olfactory bulb. These strategies are especially relevant for biologics, whose large size and chemical instability make them difficult to deliver by traditional routes.

The technology could eventually support therapies that are difficult to administer using standard nasal sprays. Small-volume devices, precision nozzles and electronically controlled applicators may improve deposition in the upper nasal cavity, while smart formulations could respond to the local environment after administration. Some future systems may combine sensing, movement and drug release in a single platform, allowing them to adapt to patient-specific conditions such as mucus composition, inflammation or variations in nasal anatomy. Such “autonomous” behavior remains largely a research goal, but it reflects a broader shift toward delivery systems that actively manage their own interaction with the body.

Despite the promise, the review emphasizes that nose-to-brain delivery is accompanied by substantial biological and engineering challenges. The nasal cavity varies considerably between individuals, and factors including age, congestion, allergies, disease, breathing patterns and prior surgery can alter deposition and absorption. Much of an intranasal dose may still be swallowed or enter the bloodstream rather than reaching the brain. Researchers must also establish whether a drug detected in brain tissue arrived through a genuine neural pathway or simply crossed the blood–brain barrier after systemic absorption. Reliable imaging, pharmacokinetic measurements and standardized animal and human models will be essential for resolving this question.

Safety is another major consideration. Repeated exposure to nanoparticles, polymers or penetration-enhancing chemicals could irritate or damage the nasal epithelium, disrupt the sense of smell or trigger immune responses. Materials must be carefully evaluated for toxicity, biodegradability and long-term accumulation. Manufacturing presents an additional hurdle: complex multifunctional carriers must be produced consistently, sterilized without losing performance and packaged in devices that deliver accurate doses. Before autonomous intranasal systems can become routine clinical tools, they will require rigorous testing in humans to demonstrate reproducible brain targeting, meaningful therapeutic benefit and acceptable safety.

The review presents intranasal delivery as more than a convenient alternative to injections. By combining biomaterials science, nanotechnology, neurobiology and device engineering, autonomous systems could create a new generation of brain-targeted medicines capable of protecting sensitive cargo, overcoming mucosal barriers and releasing therapy in response to local conditions. The field is still moving from sophisticated laboratory prototypes toward clinically validated products, but its central ambition is clear: to make treatment of the brain less invasive, more precise and more adaptable to the complex biology of each patient.

Subject of Research: Autonomous intranasal delivery systems for transporting therapeutics to the central nervous system

Article Title: Autonomous intranasal delivery systems for central nervous system therapeutics

Article References: Shen, H., Srivastava, S.K., Aggarwal, N. et al. Autonomous intranasal delivery systems for central nervous system therapeutics. Exp Mol Med (2026). https://doi.org/10.1038/s12276-026-01781-5

Image Credits: AI Generated

DOI: 10.1038/s12276-026-01781-5

Keywords: intranasal drug delivery, nose-to-brain delivery, central nervous system therapeutics, blood–brain barrier, nanomedicine, autonomous delivery systems, nanoparticles, neurotherapeutics

The mammary gland is unusual because much of its structure is assembled after birth. During puberty, ducts extend through the surrounding fat pad, while pregnancy triggers the formation of milk-producing alveoli. After lactation, much of this tissue is dismantled through a process known as involution. Mammary stem and progenitor cells must therefore operate within a tissue that repeatedly grows, differentiates, expands, and regresses. Their activity is influenced by ovarian hormones, growth factors, immune cells, extracellular matrix components, and mechanical signals from neighboring tissue.

At the center of this biology is the concept of cellular hierarchy. Mammary epithelial cells are broadly divided into basal or myoepithelial cells, which help contract the ducts, and luminal cells, which line the ducts and include milk-secreting cells. Stem-like populations and lineage-restricted progenitors can occupy different positions within this hierarchy, although modern evidence suggests that the boundaries are more flexible than once believed. Under particular developmental or damaging conditions, mature cells may change identity or regain progenitor-like properties, a phenomenon known as lineage plasticity.

This plasticity is controlled by a complex molecular network. Hormone receptors, including estrogen and progesterone receptors, transmit signals that coordinate growth with reproductive cycles. Wnt, Notch, Hedgehog, and transforming growth factor beta pathways help regulate self-renewal, differentiation, and tissue architecture. Growth factors such as epidermal growth factor and fibroblast growth factor can further alter cellular behavior. Rather than functioning independently, these pathways form interconnected signaling circuits that allow mammary cells to interpret both internal hormonal changes and external conditions in their local microenvironment.

The surrounding niche is just as important as the stem cells themselves. Fibroblasts, immune cells, blood vessels, adipocytes, and the extracellular matrix all contribute signals that can either preserve stemness or encourage differentiation. The matrix provides physical support, but it also acts as a biochemical signaling platform. Changes in its stiffness, composition, or organization can affect cell polarity, migration, and gene expression. This helps explain why a genetically normal mammary cell may behave very differently in healthy tissue compared with an inflamed, fibrotic, or tumor-associated environment.

Technological advances are now revealing this complexity at unprecedented resolution. Single-cell RNA sequencing can measure gene activity in individual cells, allowing researchers to distinguish closely related states that were previously grouped together. Spatial transcriptomics adds geographic information, showing where specific cell populations and signals are located within tissue. Lineage tracing, organoid cultures, and three-dimensional models provide complementary ways to test whether a cell can truly self-renew or generate multiple descendants. Together, these approaches are challenging the idea that one universal mammary stem-cell marker can identify every regenerative cell in every biological context.

The same flexibility that supports normal development may become dangerous when regulatory systems fail. In breast cancer, altered stem and progenitor states may help malignant cells survive treatment, seed new tumors, or spread to distant organs. Cancer stem-like cells are not necessarily a fixed population; they can emerge when tumor cells are exposed to inflammatory signals, metabolic stress, low oxygen, or chemotherapy. This reversible transition, often called phenotypic plasticity, may allow a tumor to regenerate even after most rapidly dividing cells have been eliminated.

Inflammation and aging add further layers of risk. Persistent inflammatory signaling can reshape the mammary niche and activate pathways associated with survival and proliferation. Aging may reduce regenerative capacity while increasing genomic instability and changes in the extracellular matrix. Pregnancy, obesity, endocrine disruption, and tissue injury can also modify the signals surrounding mammary stem and progenitor cells. The review emphasizes that disease cannot be understood solely by examining epithelial cells; it must also account for the ecosystem in which those cells reside.

These insights could influence future approaches to breast-cancer prevention and treatment. Instead of targeting only rapidly dividing tumor cells, researchers may need to design therapies that disrupt the signals maintaining stem-like states or restore normal differentiation programs. Potential strategies include blocking abnormal Wnt or Notch activity, modifying tumor-associated inflammation, targeting supportive stromal cells, or changing the physical properties of the tumor microenvironment. However, because the same pathways are essential for normal tissue repair, effective treatments will require precise control to avoid damaging healthy regenerative cells.

The emerging picture is both more complicated and more promising than the traditional stem-cell model. Mammary stem cells appear to be defined less by a permanent label than by their ability to respond to changing conditions. Their behavior depends on developmental stage, tissue location, hormonal state, injury, and disease. By integrating molecular biology, advanced imaging, computational analysis, and functional experiments, the field is moving toward a dynamic model of mammary regeneration. Understanding that adaptability may ultimately reveal why healthy breast tissue renews itself so effectively—and why the same regenerative machinery can, under the wrong circumstances, help disease take hold.

Subject of Research: Mammary stem cells, their role in breast development and regeneration, and their regulation in disease and breast cancer.

Article Title: Dynamics, function, and regulation of mammary stem cells in development and disease

Article References: Lee, E., Tao, Y., Wang, A.J. et al. “Dynamics, function, and regulation of mammary stem cells in development and disease.” Experimental & Molecular Medicine (2026). https://doi.org/10.1038/s12276-026-01780-6

Image Credits: AI Generated

DOI: 10.1038/s12276-026-01780-6

Keywords: Mammary stem cells, breast development, tissue regeneration, cellular plasticity, breast cancer, mammary gland, stem-cell niche, organoids, single-cell analysis, tumor microenvironment

The study was conducted by a joint team led by Minho Shong and Jinkuk Kim of KAIST’s Graduate School of Medical Science and Engineering, in collaboration with the KAIST faculty startup THOR Therapeutics. Their approach focuses on the biological circuit formed by growth differentiation factor 15, or GDF15, and its receptor, GFRAL. GDF15 is a signaling protein released in elevated amounts during several disease states, including cancer. When it reaches the hindbrain and binds to GFRAL, it activates neural pathways associated with nausea, appetite suppression and profound metabolic changes.

Cachexia is more complex than ordinary weight loss. Patients can continue losing muscle and body fat even when food intake is adequate, because cancer and the host response to cancer disrupt the systems that regulate energy use, inflammation and tissue maintenance. The resulting decline can weaken immunity, reduce mobility and make chemotherapy more difficult to tolerate. Although the syndrome affects an estimated 50 to 80 percent of people with cancer, available treatments have generally focused on stimulating appetite or providing nutritional support. Such measures may increase food intake temporarily, but they do not necessarily halt the breakdown of muscle or correct the underlying metabolic disturbance.

The KAIST researchers reasoned that the GDF15–GFRAL pathway could act as a central command system for this wasting response. GDF15 produced in the body circulates to the brainstem, where GFRAL is concentrated in a specialized region known as the area postrema and its surrounding neural circuitry. Once activated, this receptor can influence brain networks that control feeding behavior and autonomic metabolism. Rather than attempting to neutralize GDF15 throughout the body, the team chose to disable the receptor itself in the brainstem, preventing the signal from being received.

To accomplish this, the researchers developed antisense oligonucleotides, or ASOs, directed against Gfral messenger RNA. ASOs are short, chemically modified strands of nucleic acid engineered to bind a specific RNA sequence. When an ASO binds its target messenger RNA, cellular enzymes can promote its degradation or interfere with its processing, reducing production of the corresponding protein. In this case, the treatment lowered the supply of GFRAL receptors in the brainstem. The strategy therefore acts at the RNA stage, before the receptor is assembled and displayed on the surface of neural cells.

The experiments were performed in mice carrying tumors and showing established signs of cancer cachexia. This timing is important because many experimental interventions appear effective only when administered before severe wasting begins. According to the researchers, GFRAL silencing after cachexia had progressed substantially reduced the loss of muscle and fat. Treated animals also showed restoration of metabolic functions that had deteriorated during tumor growth, suggesting that the intervention did more than increase appetite. It helped interrupt the physiological program driving the breakdown of energy reserves.

The most striking result involved survival. At approximately day 50, the endpoint used in the study, about 90 percent of the mice receiving the GFRAL-targeting ASO remained alive, compared with roughly 20 percent of untreated tumor-bearing animals. The treated mice retained greater body weight and muscle mass and performed better in measures of muscle function. These findings indicate that cachexia itself can be a major determinant of outcome in cancer-bearing organisms and that blocking its central signaling pathway may provide benefits beyond nutritional improvement.

The work does not yet establish whether the same treatment will be safe or effective in people. GFRAL signaling is involved in the body’s response to circulating stress signals, and manipulating a receptor in the brainstem requires careful assessment of neurological, cardiovascular, gastrointestinal and metabolic effects. Human cancers also vary widely in their production of GDF15, tumor location and inflammatory biology. Nevertheless, the results offer a mechanistically precise alternative to therapies that merely encourage patients to eat. By targeting the receptor rather than broadly suppressing the signaling protein, the ASO approach may eventually be combined with chemotherapy, immunotherapy or other cancer treatments.

The findings, published in Cell Reports Medicine, represent an early step toward translating a brain-directed RNA therapy for cachexia. The researchers plan further preclinical studies, along with development of manufacturing and quality-control systems, with the stated goal of beginning clinical development in cancer patients by 2030. If the biology can be reproduced safely in humans, silencing GFRAL could become an adjunct treatment intended to preserve physical function, extend treatment tolerance and improve survival. For now, however, the evidence remains limited to tumor-bearing mice, and the central challenge will be determining whether a signal that can be switched off experimentally can be controlled with equal precision in patients.

Subject of Research:
An antisense oligonucleotide therapy targeting brainstem GFRAL to treat cancer-associated cachexia in tumor-bearing mice.

Article Title:
Therapeutic Gfral silencing via antisense oligonucleotides ameliorates cancer-associated cachexia and extends survival in tumor-bearing mice

Web References:
https://doi.org/10.1016/j.xcrm.2026.102939

References:
Cell Reports Medicine, published 27 July 2026. DOI: 10.1016/j.xcrm.2026.102939

Image Credits:
KAIST

Keywords:
Cancer cachexia, GFRAL, GDF15, antisense oligonucleotides, RNA therapy, brainstem, muscle wasting, cancer metabolism, preclinical research, KAIST

The phase 2 study evaluated cemiplimab and fianlimab alongside standard neoadjuvant chemotherapy. Neoadjuvant treatment is delivered before surgery, allowing physicians to measure how effectively a therapy eliminates cancer from the breast and nearby lymph nodes. Patients received weekly paclitaxel followed by doxorubicin and cyclophosphamide, while the immunotherapies were administered every three weeks. Surgery was performed after the drug treatment. The trial included adults with stage II or III disease considered at high risk of recurrence, including people with triple-negative breast cancer and those with hormone receptor–positive, HER2-negative tumors.

HER2-negative breast cancer is also described as ERBB2-negative breast cancer. ERBB2 is the gene that encodes the HER2 protein, a receptor involved in cell-growth signaling. When HER2 is overproduced, tumors can often be treated with HER2-directed drugs; when it is not, treatment generally relies on chemotherapy, endocrine therapy when hormone receptors are present, and increasingly, immunotherapy for selected patients. The I-SPY2 study was designed to identify promising combinations quickly by comparing investigational regimens with standard therapy and using early results to estimate whether a treatment might succeed in a larger phase 3 trial.

In the experimental arm, cemiplimab blocked PD-1, an inhibitory receptor on T cells. Tumors can exploit the PD-1 pathway to weaken immune-cell activity and avoid destruction. Fianlimab targeted LAG-3, another immune checkpoint that can suppress T-cell function when persistently activated. Blocking both pathways was intended to release complementary brakes on the immune response, potentially allowing immune cells to recognize and attack malignant cells more effectively than either approach alone. A total of 78 patients received the combination, while 350 participants were assigned to the control group.

The primary endpoint was pathologic complete response, or pCR, defined as the absence of residual invasive cancer in the breast and lymph nodes at surgery. Although pCR is not identical to long-term cure, it is strongly associated with a lower risk of recurrence in many high-risk breast cancers and is widely used to assess the effectiveness of preoperative treatment. Across all HER2-negative participants, the estimated pCR rate rose from 21% with standard therapy to 44% with the cemiplimab-fianlimab regimen. The result exceeded the I-SPY2 platform’s prespecified threshold for predicted success in a future phase 3 study.

The apparent benefit was observed in both major disease subgroups. Among patients with triple-negative breast cancer, the estimated pCR rate increased from 29% with standard therapy to 53% with the dual-immunotherapy regimen. In hormone receptor–positive, HER2-negative disease, the rate rose from 14% to 36%. These results suggest that combined checkpoint inhibition may have activity beyond tumors traditionally considered most responsive to immunotherapy. However, the study was not designed to establish definitive survival advantages, and the investigators emphasized that the exact regimen should not be adopted as a new standard based on these findings alone.

Tumor biology appeared to influence the magnitude of response. Patients whose tumors were positive for ImPrint, a 53-gene test designed to identify an immune-responsive tumor environment, experienced particularly high pCR rates after receiving the experimental treatment. The estimated rate reached 83% among ImPrint-positive patients with triple-negative disease and 91% among those with hormone receptor–positive, HER2-negative tumors. ImPrint-positive tumors show gene-expression patterns associated with immune-cell activity and a microenvironment that may be more receptive to immune stimulation. The findings support the broader goal of matching immunotherapy to the molecular features of each patient’s tumor.

The safety results nevertheless placed important limits on the treatment’s future development. Decreased adrenal hormone production occurred in 21% of patients receiving the dual-checkpoint combination, including grade 3 or 4 events in 11%. Diabetes developed in 4% of participants. These endocrine toxicities can require long-term hormone replacement or specialist care, and some emerged weeks after immunotherapy had ended. The delayed timing illustrates why patients receiving checkpoint inhibitors need continued monitoring after treatment, even when chemotherapy and surgery have been completed. The investigators concluded that the efficacy signal was compelling but that the toxicity profile was too concerning for the regimen to advance unchanged.

Claudine Isaacs, MD, lead author and associate director for clinical research at Georgetown’s Lombardi Comprehensive Cancer Center, said the results establish a proof of principle for targeting two immune checkpoints at once. Future studies may examine different doses, schedules, or newer drugs designed to hit both pathways with a potentially lower toxicity burden. One possibility is the use of bispecific antibodies, engineered molecules that bind two targets through a single drug. The I-SPY2 platform, which has enrolled more than 2,500 patients and tested 25 therapies over approximately 15 years, will continue evaluating treatment combinations and molecular tests intended to maximize benefit while limiting unnecessary harm.

Subject of Research: People

Article Title: Cemiplimab and Fianlimab With Neoadjuvant Chemotherapy in Early-Stage High-Risk ERBB2-Negative Breast Cancer: The I-SPY2 Randomized Clinical Trial

News Publication Date: 30-Jul-2026

Web References: https://doi.org/10.1001/jamaoncol.2026.2576; ClinicalTrials.gov identifier NCT01042379

References: JAMA Oncology, DOI: 10.1001/jamaoncol.2026.2576

Keywords: breast cancer, HER2-negative breast cancer, ERBB2, immunotherapy, cemiplimab, fianlimab, PD-1, LAG-3, neoadjuvant chemotherapy, pathologic complete response, I-SPY2, precision medicine

Researchers from Sun Yat-sen University Cancer Center and collaborating institutions have constructed what they describe as the first systematic pan-cancer single-cell atlas of tumor angiogenesis. The team analyzed approximately 1.24 million individual cells from 381 tumor samples representing 13 common cancer types, including breast, colorectal, gastric, liver, and lung cancers. By examining gene activity cell by cell, the investigators mapped the cellular networks that promote abnormal blood-vessel formation across diverse malignancies.

Angiogenesis is essential for tumors that outgrow the oxygen and nutrients available through diffusion. Cancer-associated blood vessels are typically disorganized, leaky, and structurally unstable, creating regions of hypoxia that can further alter tumor and stromal cells. Drugs such as bevacizumab and other anti-VEGFR therapies interfere with this process by blocking signals that stimulate endothelial cells, the cells lining blood vessels. Although these treatments can slow disease in some patients, their benefits are often temporary, and resistance is common.

The new atlas revealed that pericytes and the molecules they release are strongly associated with angiogenic activity across cancer types. Pericytes normally wrap around microvessels and help regulate vascular stability, permeability, and blood flow. Within tumors, however, these cells can be reprogrammed by abnormal signaling and a hostile microenvironment. The researchers identified a distinct population known as MCAM-positive immature pericytes, or MCAM+ imPCs, which emerged as a major source of two potent pro-angiogenic factors: placental growth factor, known as PGF, and angiopoietin-2, or ANGPT2.

PGF and ANGPT2 can support blood-vessel growth through pathways that are not fully dependent on VEGF. ANGPT2, in particular, can destabilize existing vessels and make them more responsive to additional angiogenic signals, while PGF can promote endothelial-cell activation and vascular remodeling. The study indicates that MCAM+ imPCs are shaped by dysregulated Notch signaling and hypoxic stress in the tumor microenvironment. In effect, these cells appear to function as an alternative angiogenic engine, allowing tumors to maintain or restore vascular growth despite VEGF pathway inhibition.

Laboratory experiments provided evidence that the MCAM+ imPC population is not merely correlated with treatment failure but actively contributes to it. In cell-based and animal studies, the pericytes stimulated alternative vascular responses and reduced the effectiveness of anti-VEGFR treatment. Clinical analyses reinforced the finding. Among patients with ovarian cancer, urothelial cancer, and glioblastoma who received bevacizumab, higher levels of MCAM+ imPCs were associated with shorter overall survival and progression-free survival. These observations suggest that the abundance of these cells could eventually serve as a biomarker for identifying tumors likely to resist anti-angiogenic therapy.

The investigators then tested a strategy designed to eliminate the cellular source of the resistance signals. They developed an MCAM-targeting antibody-drug conjugate, or ADC, capable of recognizing the MCAM protein on the surface of the immature pericytes and delivering a cytotoxic payload. Rather than blocking a single secreted factor, the approach is intended to remove the pro-angiogenic cell population responsible for producing PGF and ANGPT2. This distinction could be important because tumor cells and stromal cells often compensate when one signaling molecule is inhibited.

When the MCAM ADC was combined with anti-VEGFR therapy, the treatment produced stronger suppression of angiogenesis and tumor growth than either treatment alone in mouse models of breast, renal, and lung cancers. The researchers describe the approach as dual endothelial-cell and pericyte inhibition. Anti-VEGFR drugs primarily disrupt signaling to endothelial cells, while the ADC targets the pericyte compartment that supports alternative vessel formation. By attacking both parts of the tumor vascular system, the combination may make it more difficult for tumors to bypass treatment.

Safety studies in the experimental models also produced encouraging results. The MCAM ADC did not cause significant changes in body weight, blood-cell counts, liver function, kidney function, or blood-brain barrier integrity. These findings do not establish clinical safety, but they provide preliminary support for further development. A humanized version of the therapy, AMT-253, is already being evaluated in a first-in-human Phase I trial listed under ClinicalTrials.gov identifier NCT05906862. Early-stage trials are primarily designed to assess safety, dosing, and tolerability rather than to prove effectiveness.

The study reframes anti-angiogenic resistance as a problem involving more than endothelial cells and VEGF. It suggests that the tumor microenvironment contains specialized support cells capable of preserving vascular growth through parallel molecular routes. If the findings are confirmed in larger clinical studies, MCAM+ immature pericytes could become both a therapeutic target and a predictive marker for anti-angiogenic treatment. The researchers say their pan-cancer atlas and dual-targeting strategy may help guide more durable vascular therapies, although the clinical value of MCAM ADCs will depend on results from ongoing human trials.

The work was led by Professors Xu Ruihua, Liu Zexian, and Luo Huiyan of Sun Yat-sen University Cancer Center, who served as co-corresponding authors. Dr. Zheng Yongqiang, Dr. Sun Hui, Dr. Fu Zhe, Dr. Chen Haojie, and Dr. Cai Guangyao were listed as co-first authors. The research was supported by Chinese national, provincial, and institutional funding programs, including the National Key R&D Program of China, the National Natural Science Foundation of China, and programs supporting young investigators and postdoctoral researchers.

Subject of Research: Tumor angiogenesis, anti-angiogenic therapy resistance, MCAM-positive immature pericytes, and MCAM-targeting antibody-drug conjugates.

Web References: https://doi.org/10.1016/j.scib.2026.06.022; ClinicalTrials.gov identifier NCT05906862

References: Science Bulletin, DOI: 10.1016/j.scib.2026.06.022

Image Credits: © Science Bulletin / Authors

Keywords: cancer research, tumor angiogenesis, pericytes, VEGF, anti-angiogenic therapy, bevacizumab, MCAM, MCAM ADC, AMT-253, PGF, ANGPT2, cancer drug resistance, single-cell analysis, tumor microenvironment, antibody-drug conjugate

DNA is continuously damaged by environmental chemicals, radiation, metabolic by-products, and mistakes made during replication and cell division. If these lesions are not repaired accurately, they can cause mutations, chromosome rearrangements, or cell death, contributing to diseases including cancer. Human cells therefore rely on several specialised repair pathways, each adapted to a particular form of damage. These include pathways that correct small chemical alterations in DNA, repair breaks in one or both strands, and restore damaged replication structures. The new work indicates that the availability of many of the proteins involved in these pathways is regulated outside the nucleus.

The study was conducted by researchers in Rainer Pepperkok’s group at EMBL Heidelberg, in collaboration with the Human Protein Atlas and Emma Lundberg’s laboratory at Stanford University. The researchers examined where proteins are located within human cells, focusing on proteins that appeared in both the Golgi complex and the nucleus. Best known as the cell’s processing and distribution hub, the Golgi modifies proteins, sorts them, and packages them for delivery to different cellular destinations. Its newly identified connection with genome maintenance expands the organelle’s role far beyond intracellular shipping.

The initial protein-localisation screen revealed more than 300 proteins shared between the Golgi and the nucleus. Among them was a broad collection of DNA-repair factors representing almost every major repair pathway. Their presence at the Golgi was not simply a fixed consequence of protein production. When the researchers exposed cells to chemical agents that cause different types of DNA damage, the proteins changed location in a damage-specific manner. Factors required to address a particular lesion moved from the Golgi into the nucleus, while proteins not needed for that response were removed from the nucleus and sequestered at the Golgi.

This pattern suggests that the Golgi functions as a dynamic reservoir for repair machinery. Rather than allowing all DNA-repair proteins to circulate freely through the nucleus, the cell may limit access to specific factors until they are needed. Such spatial control could help organise the DNA-damage response, reduce inappropriate activity, and ensure that repair proteins are deployed in the correct combination. The discovery also points to a wider principle in cell biology: organelles traditionally assigned to cytoplasmic functions may directly influence nuclear processes through the regulated movement of proteins.

The researchers investigated this mechanism in greater detail using RAD51C, a protein essential for homologous recombination. This repair pathway is particularly important for correcting DNA double-strand breaks, among the most dangerous forms of genomic damage. Homologous recombination uses an intact DNA sequence as a template to restore the correct genetic information, helping cells repair breaks with relatively high accuracy. RAD51C also has clinical importance because inherited or acquired mutations in the gene are associated with elevated risks of cancers including breast and ovarian cancer.

Under normal conditions, RAD51C was retained at the Golgi through an interaction with Giantin, a large structural protein that helps organise the Golgi membrane system. After DNA damage occurred, RAD51C was released from this Golgi-associated pool and moved into the nucleus. There, it accumulated at sites where DNA repair was taking place. When the researchers removed Giantin, RAD51C localisation was disrupted, and the cells were unable to complete the normal repair response. These results link the physical organisation of the Golgi directly to the functional activity of a DNA-repair pathway.

The findings imply that damage-induced relocation is not merely a passive redistribution of proteins. Instead, the Golgi appears to participate in the timing and selection of the cellular response. A damaged cell must rapidly identify the nature of a lesion, mobilise the appropriate repair factors, and prevent conflicting or unnecessary activities. By holding proteins in a defined cytoplasmic compartment and releasing them in response to specific signals, the Golgi may provide an additional layer of regulation. The molecular signals that trigger this release, and the mechanisms that return proteins to the Golgi after repair, remain important questions for future research.

The study also raises the possibility that the Golgi–nucleus connection affects more than DNA repair. The proteins shared between the two organelles were involved in numerous cellular pathways, suggesting that communication between the Golgi and the nucleus is extensive. Changes in Golgi structure or trafficking could therefore influence gene stability, stress responses, and disease processes in ways that have not yet been recognised. Because defects in DNA repair are a defining feature of many cancers, understanding how repair proteins are stored and deployed could eventually inform the development of diagnostic tools or treatments that target cellular organisation as well as the repair enzymes themselves.

By identifying the Golgi as an active participant in the DNA-damage response, the EMBL team has expanded the concept of genome protection from a strictly nuclear operation to a coordinated process involving the entire cell. The work presents the Golgi as a staging area that can store repair factors, control their release, and help determine when they reach damaged DNA. It also reinforces a growing view of the cell as an interconnected system in which cytoplasmic organelles and the nucleus continuously exchange information. Further research will be needed to determine whether similar control mechanisms operate in other organelles and how their failure might contribute to human disease.

Subject of Research: DNA repair regulation and communication between the Golgi complex and the nucleus

News Publication Date: 28-Jul-2026

Web References: https://doi.org/10.1083/jcb.202605024

References: Journal of Cell Biology, DOI: 10.1083/jcb.202605024

Image Credits: Karolina Kuodyte/EMBL

Keywords: DNA repair, Golgi apparatus, RAD51C, Giantin, homologous recombination, DNA damage response, cancer biology, cell biology, nuclear-cytoplasmic communication

CUP is not a single disease but a clinical condition in which cancer has spread while its original site remains hidden. In many patients, doctors use imaging, pathology, immunohistochemistry and molecular tests to search for the primary tumour. Even after extensive investigation, however, the source may remain unknown. This creates a major treatment challenge because cancer therapies are often selected according to the tissue in which a tumour originated. A cancer that began in the lung, breast, bowel or pancreas may respond to very different drugs, yet CUP can prevent clinicians from making that distinction with confidence.

The CUP-COMP trial is focused on a technology known as liquid biopsy. Instead of requiring a tumour sample obtained through surgery or an invasive biopsy, liquid biopsy analyses biological material circulating in the blood. Tumour cells can release fragments of DNA into the bloodstream, including circulating tumour DNA, or ctDNA. These fragments may contain mutations, copy-number changes and other molecular abnormalities that reflect the biology of the cancer. By sequencing this material, researchers can search for patterns that may help classify a tumour, reveal potentially targetable alterations or indicate how the disease is changing over time.

The central question is not simply whether such a test can produce a technically impressive molecular profile. The trial is designed to investigate whether blood-based profiling can be delivered reliably and usefully in routine clinical pathways for patients with CUP. That distinction is crucial. A test may work in a laboratory but prove difficult to implement at a national scale if blood samples arrive too late, contain too little tumour-derived DNA, fail quality-control checks or produce results that clinicians cannot interpret within the time available for treatment decisions.

A prospective design allows the researchers to evaluate these issues as they occur, rather than relying only on stored samples or retrospective records. Patients can be followed through the process of consent, blood collection, sample transport, laboratory analysis and clinical reporting. This approach can reveal where delays and failures arise and whether the information generated is available at a moment when it might influence patient care. It also provides a framework for measuring how often blood samples yield an interpretable molecular profile and how consistently testing can be integrated across participating centres.

Technically, the approach may combine several layers of genomic information. DNA sequencing can identify mutations in genes that drive tumour growth or create vulnerabilities to targeted drugs. Copy-number analysis can detect gains and losses of DNA segments, while broader molecular signatures may offer clues about tumour lineage. Some platforms can also estimate the fraction of DNA in a blood sample that originates from the tumour, a measurement known as tumour fraction. When this fraction is low, a negative result may not mean that a mutation is absent; it may simply indicate that the test did not receive enough tumour-derived material to detect it.

That limitation is particularly important in CUP, where disease biology can vary widely and metastatic deposits may release unequal amounts of DNA into the circulation. Tumour burden, the location of metastases, treatment exposure and the biology of individual cancers can all affect ctDNA levels. Blood-based profiling therefore does not eliminate the need for clinical assessment, imaging or tissue pathology. Instead, it is being evaluated as an additional source of evidence that could complement established diagnostic methods and potentially reduce the time required to obtain molecular information.

The precision-medicine element of CUP-COMP reflects a broader shift in cancer treatment. Rather than assigning therapy solely according to the organ where a tumour started, oncologists increasingly seek molecular features that can be targeted directly. Alterations in genes involved in DNA repair, cell signalling or immune regulation may appear across cancers from different organs. If these abnormalities are detected in a patient with CUP, they could provide a rationale for considering a targeted therapy or an immunotherapy, although the clinical value of any proposed treatment must still be assessed through evidence, eligibility criteria and multidisciplinary review.

The study also addresses an important question of equity and scalability. Advanced molecular testing is not useful if it is available only at specialist institutions or to patients who can access highly centralised services. A national trial can test whether samples collected in different hospitals can be processed through a coordinated system and whether results can be returned in a consistent format. The findings may help establish the logistical requirements for wider adoption, including laboratory capacity, data interpretation, reporting standards and communication between molecular scientists and treating teams.

For patients facing a diagnosis in which the primary tumour cannot be found, the promise of a blood-based test is therefore measured not only in scientific novelty but in speed, accessibility and clinical clarity. CUP-COMP is evaluating whether molecular information can be obtained from a relatively simple blood draw and incorporated into real-world decision-making. Its significance will ultimately depend on whether the approach produces dependable results, identifies actionable biology and fits the demanding timelines of cancer care. By testing those questions prospectively, the study may help determine whether liquid biopsy can become a practical component of precision medicine for one of oncology’s most uncertain and difficult diagnoses.

Subject of Research: Blood-based molecular profiling and precision medicine for patients with Cancer of Unknown Primary (CUP).

Article Title: A prospective national precision medicine trial evaluating the feasibility of blood-based molecular profiling in patients with Cancer of Unknown Primary (CUP-COMP).

Article References: Conway, AM., Robinson, M., Concannon, M. et al. A prospective national precision medicine trial evaluating the feasibility of blood-based molecular profiling in patients with Cancer of Unknown Primary (CUP-COMP). Br J Cancer (2026). https://doi.org/10.1038/s41416-026-03519-6

Image Credits: AI Generated

DOI: 10.1038/s41416-026-03519-6

Keywords: Cancer of Unknown Primary, CUP, liquid biopsy, circulating tumour DNA, molecular profiling, precision medicine, cancer genomics, oncology, blood-based testing.

The study examined health records from nearly 16,000 women in Ontario who underwent BRCA testing between 2007 and 2016. The participants were not randomly selected from the general population. Most had been referred for testing because of a personal or family history of breast, ovarian or related cancers, a known mutation in their family, or ancestry associated with elevated hereditary cancer risk. This distinction is important: a negative result in a woman already considered high risk does not necessarily erase the clinical information that prompted testing in the first place.

BRCA1 and BRCA2 are tumor-suppressor genes involved in repairing damaged DNA. When certain inherited mutations impair their function, cells can accumulate genetic errors more readily, increasing the probability that a tumor will develop. Women carrying a harmful mutation in one of these genes may face a lifetime breast cancer risk estimated at roughly 30% to 70%, depending on the gene, the specific variant and other biological and environmental factors. Yet the absence of a detectable mutation does not mean that all inherited or familial risk has been excluded.

Among women in the Ontario cohort who tested negative for a pathogenic BRCA mutation, the estimated lifetime risk of breast cancer was 25%. The estimated risk was even higher—30%—for women whose test revealed a variant of uncertain significance, or VUS. A VUS is a genetic alteration for which available evidence is insufficient to determine whether it affects gene function or cancer susceptibility. Such findings are not considered proof of increased risk and generally should not be used alone to guide irreversible medical decisions, but the women in this study remained part of a clinically high-risk population because of the circumstances that led to testing.

The researchers also found that family history substantially changed risk estimates within every genetic test category. Among women who tested positive for a BRCA mutation, lifetime breast cancer risk ranged from approximately 56% to 86%, depending on how many first-degree relatives had been diagnosed with breast or ovarian cancer. First-degree relatives include parents, siblings and children, whose shared genetic background provides a particularly informative measure of inherited susceptibility. The results reinforce the idea that a genetic test is not a complete risk assessment; it is one component of a broader calculation that includes family patterns, age, reproductive history and other factors.

“The future cancer risk for these women has not been well studied,” said Fahima Dossa, MD, PhD, a surgical oncologist at Cedars-Sinai Cancer and lead author of the study. She said the findings could help clinicians guide all women who undergo BRCA testing, rather than treating a negative result as a universal return to average risk. In practical terms, physicians may combine genetic findings with detailed family histories and validated risk models to determine whether a patient needs earlier or more frequent mammography, supplemental breast MRI, genetic counseling or discussion of preventive options.

The study illustrates why a negative result can have different meanings depending on the reason for testing. A woman who has a known familial BRCA mutation and tests negative specifically for that mutation may have a risk closer to that of the general population, because the familial cause has been identified and excluded for her. By contrast, a woman with several close relatives affected by breast cancer who receives a negative result on a broader BRCA test may still carry other inherited risk factors that current testing did not detect or that have not yet been scientifically characterized.

For patients, the distinction between “negative,” “uninformative negative” and “variant of uncertain significance” can be crucial. A negative result means that no harmful mutation covered by the test was identified, not that the person has no genetic susceptibility. An uninformative negative result occurs when testing fails to explain a strong family cancer pattern. Genetic counseling can help determine whether additional testing, updated analysis or screening based on family history is appropriate. At the same time, the researchers emphasize that test results should be interpreted by qualified clinicians and should not automatically lead to preventive surgery or other major interventions.

The study was supported by ICES, the Ontario Ministry of Health and Ministry of Long-Term Care, the Canadian Cancer Society and the Canadian Institutes of Health Research. Its observational design means that it can estimate cancer incidence within a large tested population but cannot prove that family history alone caused the elevated risk. The findings nevertheless provide new evidence that hereditary cancer assessment must move beyond a single gene result. As genetic testing expands, the central message is becoming increasingly difficult to ignore: a negative BRCA test may close one investigative path, but it does not necessarily close the question of breast cancer risk.

Subject of Research: Breast and ovarian cancer risk among women undergoing BRCA1 and BRCA2 genetic testing

Article Title: Incidence of Breast and Ovarian Cancer Among Women Undergoing BRCA1 and BRCA2 Testing

News Publication Date: 30-Jul-2026

Web References: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2026.26334

References: Dossa F, Metcalfe K, Ante Z, Liu N, Lerner-Ellis J, Eisen A, Baxter NN. “Incidence of Breast and Ovarian Cancer Among Women Undergoing BRCA1 and BRCA2 Testing.” JAMA Network Open. DOI: 10.1001/jamanetworkopen.2026.26334

Keywords: BRCA1, BRCA2, breast cancer, ovarian cancer, genetic testing, hereditary cancer, family history, variant of uncertain significance, cancer risk, genetic counseling

Primary plasma cell leukemia develops when abnormal plasma cells, the antibody-producing cells of the immune system, escape the bone marrow and circulate in large numbers through the blood. Unlike the more common form of multiple myeloma, plasma cell leukemia often advances rapidly and is associated with extensive disease burden, organ complications and early relapse. Approximately 1,200 new cases are diagnosed in the United States each year, making large clinical studies difficult to conduct. The QUANTUM Trial is therefore intended to address a major unmet need in a patient population that has historically been excluded from or underrepresented in many cancer trials.

The study will begin with an intensive four-drug induction regimen known as D-KRd. Patients will receive daratumumab, carfilzomib, lenalidomide and dexamethasone for four cycles. Each component attacks the cancer through a different biological pathway. Daratumumab binds to CD38, a protein found at high levels on plasma cells, and helps recruit immune mechanisms against those cells. Carfilzomib blocks the proteasome, an intracellular waste-processing system that malignant plasma cells depend on to survive. Lenalidomide modifies immune activity and disrupts the tumor-supporting environment, while dexamethasone directly contributes to plasma-cell death and helps control inflammation.

After induction, participants will undergo stem cell mobilization and collection followed by high-dose chemotherapy and autologous stem cell transplantation. In this procedure, a patient’s own blood-forming stem cells are collected before intensive chemotherapy and then returned to help restore bone marrow function. The high-dose treatment is intended to eliminate as much residual leukemia as possible, but transplantation alone does not guarantee that microscopic disease has been eradicated. For patients with primary plasma cell leukemia, remaining malignant cells can expand quickly, making the period immediately after transplantation a critical opportunity for additional therapy.

The central question of QUANTUM begins after transplantation, when participants will be randomly assigned to one of two consolidation strategies. Patients in the experimental group will receive teclistamab, while those in the standard-treatment group will continue D-KRd therapy. Consolidation therapy is administered after initial treatment to deepen a response and eliminate residual cancer cells that may not be detectable through routine testing. Investigators will evaluate whether teclistamab-based consolidation can improve overall survival compared with continued quadruplet therapy in this high-risk disease.

Teclistamab is a bispecific antibody engineered to connect malignant plasma cells with T cells, the immune system’s specialized cellular killers. One end of the drug binds to B-cell maturation antigen, or BCMA, a surface protein commonly expressed by plasma cells and plasma-cell cancers. The other end binds to CD3 on T cells. By physically bringing the two cell types together, teclistamab can activate T cells against BCMA-positive cancer cells, prompting the release of cytotoxic molecules that damage and destroy the malignant cells. The approach is distinct from conventional chemotherapy because it relies on redirecting a patient’s immune cells rather than simply exposing rapidly dividing cells to a toxic drug.

Teclistamab is already approved for certain patients with multiple myeloma, particularly those whose disease has returned or stopped responding after several previous treatments. Its use in newly diagnosed primary plasma cell leukemia, and specifically as post-transplant consolidation, remains investigational. The QUANTUM Trial will help determine whether the drug’s immune-targeting activity can be deployed earlier in the disease course, when the number of malignant cells may be lower and the immune system may have a better chance of controlling residual disease. Because T-cell activation can also produce serious inflammatory or neurological complications, participants will be closely monitored for treatment-related effects.

Following the consolidation phase, patients in both study groups will receive maintenance treatment with carfilzomib and lenalidomide. Maintenance therapy is intended to suppress surviving malignant plasma cells over the long term and delay recurrence. The trial’s sequential design reflects the complexity of treating plasma cell leukemia: rapid disease reduction is pursued with induction therapy, intensive treatment is used to achieve deeper remission, randomized consolidation tests the new immune-based strategy, and maintenance seeks to preserve disease control. Researchers will compare outcomes between the two groups, with overall survival serving as a key measure of whether the experimental approach produces a meaningful benefit.

The National Cancer Institute is sponsoring the Phase II study, which is being conducted through the Alliance for Clinical Trials in Oncology and is expected to enroll 74 adults at participating cancer centers and medical clinics across the United States. “Plasma cell leukemia progresses rapidly and remains one of the most difficult blood cancers to treat effectively,” said Douglas Sborov, MD, MS, professor of medicine at the University of Utah-Huntsman Cancer Institute and principal investigator of the trial. He said the study aims to use teclistamab after transplantation to harness patients’ own immune systems against residual cancer cells and ultimately improve long-term survival. The trial’s findings could help clarify whether bispecific antibody therapy belongs earlier in the treatment pathway for one of hematology’s most dangerous malignancies.

Article Title: QUANTUM Trial Tests Teclistamab After Stem Cell Transplantation for Primary Plasma Cell Leukemia

Web References: https://clinicaltrials.gov/study/NCT07605416

References: Alliance A062401—Quadruplet Induction Followed by Teclistamab Consolidation and Doublet Maintenance in Patients with Primary Plasma Cell Leukemia: The QUANTUM Trial

Image Credits: Alliance for Clinical Trials in Oncology

Keywords: Primary plasma cell leukemia, plasma cell leukemia, teclistamab, bispecific antibody, BCMA, T-cell immunotherapy, multiple myeloma, stem cell transplantation, autologous transplant, daratumumab, carfilzomib, lenalidomide, dexamethasone, cancer clinical trial, hematology, oncology, cancer immunotherapy, QUANTUM Trial, Alliance for Clinical Trials in Oncology, National Cancer Institute

In chronic lymphocytic leukemia (CLL), scientists investigated why some patients eventually stop responding to BTK degraders, a newer class of drugs designed to destroy the BTK protein rather than merely block its activity. BTK is part of a signaling pathway that helps malignant B cells survive and multiply. Early trials of degraders such as zelebrudomide and bexobrutideg produced response rates above 80% among patients whose disease had already resisted other therapies, but resistance still emerged in some cases.

By analyzing tumor samples from treated patients, an MSK-led team identified a mutation known as BTK A428D in several tumors that became resistant. The mutation was not necessarily created by treatment; in some patients, small populations of A428D cells were already present before therapy began. As the degrader eliminated drug-sensitive leukemia cells, those resistant cells gained a competitive advantage and expanded. The researchers found that venetoclax, an established leukemia drug, could be combined with BTK degraders to target both mutant and nonmutant cancer cells in laboratory experiments, raising the possibility of a future clinical trial.

Another MSK study examined why bone is such a challenging destination for metastatic cancer. The researchers found that the physical hardness of bone may act as an immune warning signal. When cancer cells encounter a rigid environment, they become mechanically stiffer. That change can make them more vulnerable to natural killer cells and cytotoxic T cells, immune cells that destroy abnormal targets by releasing toxic molecules and triggering cell death. In mouse models, animals lacking effective immune defenses developed extensive bone metastases, while animals with intact natural killer and T-cell responses largely resisted colonization.

The investigators also identified osteopontin, or SPP1, as a critical molecule in the process. Cancer cells producing high levels of osteopontin were better able to adapt to bone-forming environments and establish metastatic sites. Human melanoma data added a surprising layer: tumors with high osteopontin activity and mechanically stiff cancer cells often contained fewer immune cells. The researchers interpret this pattern as evidence of “mechanosurveillance,” in which immune cells respond not only to chemical signals but also to the physical properties of cancer cells. In tumors with strong immunity, stiff cells may be eliminated; where immune defenses are weak, they can survive and accumulate.

Smoking cessation was the focus of a randomized trial involving 306 people diagnosed with cancer within the previous four months. Conducted through ECOG-ACRIN and co-led by MSK and Mass General Brigham investigators, the trial compared usual care with a sustained telehealth intervention. Patients in the intervention group received as many as 11 video counseling sessions addressing motivation, cravings, stress management, and relapse prevention, along with free nicotine patches and lozenges for up to 12 weeks. After six months, 28% had stopped using tobacco, compared with 15% who received only information about quitline and cessation resources. The program also helped many participants who did not quit completely reduce their daily tobacco use, demonstrating that virtual support can reach patients treated in community hospitals far from major cancer centers.

At the molecular level, MSK structural biologists produced the first detailed three-dimensional images of SLC34A2, a transporter that controls phosphate movement across cell membranes. Phosphate is essential for energy metabolism, bone formation, and cellular signaling, but excessive blood phosphate can contribute to kidney failure, cardiovascular damage, and abnormal calcium deposits. Using cryo-electron microscopy, the researchers captured the transporter in several functional states and discovered that it operates differently from the classic “alternating access” mechanism used by many membrane transporters.

Rather than moving its phosphate-binding region back and forth across the membrane, SLC34A2 appears to keep that region relatively stable while a surrounding gate opens and closes. This structural information shows how an existing inhibitor binds to the transporter and could help researchers design more precise drugs. SLC34A2 is overproduced in an estimated 80% to 90% of ovarian tumors and is being investigated as a therapeutic target. The protein is also relevant to chronic kidney disease, which affects more than 800 million people worldwide and is often associated with disrupted phosphate regulation.

A separate analysis of more than 35,000 cancer patients examined whether Medicare Advantage insurance affects the quality, speed, or cost of cancer care. The investigators compared patients enrolled in Medicare Advantage with those receiving traditional Medicare across 13 treatment scenarios, including metastatic colon cancer, multiple myeloma, and advanced prostate cancer. They evaluated actual treatments against National Comprehensive Cancer Network guidelines and linked those treatments to Medicare reimbursement data. Medicare Advantage patients were just as likely to receive guideline-concordant care, and treatment began after a median of 36 days, compared with 35 days for traditional Medicare. At the same time, estimated treatment costs were about 6% lower, or approximately $931 per patient, suggesting that savings may come from selecting less expensive options that remain clinically appropriate rather than from reducing treatment quality.

MSK neurosurgeons also investigated how much brain tissue should be removed when tumors cause temporal-lobe epilepsy. These tumors can trigger recurrent seizures, but aggressive surgery may damage regions involved in language and memory. Reviewing seven studies involving 277 patients, the researchers found that complete removal of the tumor itself was the strongest predictor of seizure control. Patients with only partial tumor removal were more likely to experience continuing seizures and tumor regrowth. Removing additional healthy brain tissue beyond the lesion, however, did not consistently improve seizure outcomes. Cognitive effects varied, although removal of the entire hippocampus, tumors on the left side of the brain, and deeply located temporal tumors were associated with greater risks to verbal memory.

Together, the findings illustrate how modern cancer research is expanding beyond the search for new drugs. Resistance can arise from rare mutant cells already hidden within a tumor; metastatic disease can be shaped by the mechanical stiffness of tissue; and immune cells may read physical signals as readily as molecular ones. At the same time, behavioral programs delivered through video technology, structural images of membrane proteins, carefully measured insurance outcomes, and more conservative surgical strategies are opening additional paths toward more effective and safer care.

Subject of Research: Cancer biology, leukemia drug resistance, bone metastasis, tobacco cessation, phosphate transport, cancer care costs, and epilepsy surgery.

Article Title: Memorial Sloan Kettering Research Reveals New Insights Into Drug-Resistant Leukemia, Bone Metastasis, Smoking Cessation, Phosphate Transport, Cancer Care, and Tumor-Related Epilepsy

Web References: https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-26-0251/786984/Molecular-and-Structural-Basis-of-Pan-Resistance; https://www.cell.com/immunity/fulltext/S1074-7613(26)00276-1; https://ascopubs.org/doi/abs/10.1200/JCO-25-02267; https://www.pnas.org/doi/abs/10.1073/pnas.2602077123; https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2851378; https://www.sciencedirect.com/science/article/pii/S1525505026002891

References: Cancer Discovery; Immunity; Journal of Clinical Oncology; Proceedings of the National Academy of Sciences; JAMA Internal Medicine; Epilepsy & Behavior.

Image Credits: Memorial Sloan Kettering Cancer Center

Keywords: Cancer research, chronic lymphocytic leukemia, BTK degraders, BTK A428D, venetoclax, bone metastasis, osteopontin, mechanosurveillance, immunology, smoking cessation, telehealth, SLC34A2, phosphate transporter, ovarian cancer, kidney disease, Medicare Advantage, epilepsy surgery, brain tumors