At the heart of this research lies the dynamic crosstalk between macrophages, a type of immune cell, and malignant breast cancer cells. Macrophages, traditionally known for their role in immune defense and tissue homeostasis, can, paradoxically, be co-opted by tumors to bolster their survival during chemotherapy. The study meticulously elucidates how these cells communicate, adapt, and ultimately promote drug resistance, highlighting the sophisticated cellular choreography underpinning treatment failure.

The researchers employed cutting-edge molecular and cellular biology techniques, combining in vitro co-culture systems with transcriptomic analyses and advanced imaging, to dissect the bidirectional communication pathways. Their data reveal that tumor-associated macrophages (TAMs) release a repertoire of cytokines and growth factors that activate survival pathways in cancer cells. Conversely, cancer cells secrete signals that reprogram macrophages into a pro-tumoral phenotype, reinforcing the vicious cycle of therapy evasion.

Central to this resistance mechanism is the secretion of interleukin-6 (IL-6) and transforming growth factor-beta (TGF-β) by macrophages, which engage STAT3 signaling and epithelial-to-mesenchymal transition (EMT) programs within cancer cells. Activation of STAT3 is particularly notorious for promoting cell survival and stem-like traits, which are directly linked to reduced sensitivity to chemotherapeutic agents. This bidirectional signaling establishes a microenvironment that favors tumor persistence despite aggressive chemotherapy.

The significance of EMT induction cannot be overstated, as it endows cancer cells with enhanced motility and invasiveness, traits correlative with metastatic potential and severe therapeutic resistance. The study’s authors emphasize that interrupting this crosstalk could recalibrate the tumor microenvironment, rendering cancer cells more susceptible to treatment and curbing metastatic dissemination.

Moreover, the research sheds light on the metabolic adaptations that accompany this macrophage-cancer cell interaction. Macrophages modulate the metabolic landscape to support tumor survival by increasing the availability of nutrients and modulating the acidic microenvironment, which further diminishes chemotherapy efficacy. These findings suggest that targeting metabolic pathways may represent a promising adjunct strategy alongside conventional chemotherapy.

The observation that macrophage-cancer cell communication fuels resistance challenges prior paradigms that regarded macrophages solely as cancer-fighting immune cells. Instead, it highlights a dualistic role shaped by the tumor milieu, underscoring the complexity of cellular interactions within cancer’s ecosystem. This duality necessitates innovative therapeutic approaches that can re-educate or inhibit macrophages selectively without compromising systemic immunity.

Importantly, the study underscores the heterogeneity of macrophage populations in tumors, whereby different subsets possess distinct functional properties, ranging from tumoricidal to tumor-supportive activities. Precision targeting of specific macrophage subsets or their signaling mediators could enhance therapeutic specificity and minimize off-target effects, a critical consideration for future drug development.

From the translational perspective, the identification of the key molecular players within this crosstalk creates prospects for biomarker development. Measuring levels of macrophage-derived cytokines or signaling intermediates could serve as predictive markers for chemotherapy response, enabling personalized treatment regimens that anticipate resistance and adjust strategies proactively.

The research also offers promising leads for combination therapies that co-target cancer cells and the supportive macrophage environment. For example, pharmacologic inhibitors of STAT3 or blocking antibodies against IL-6 or TGF-β pathways could sensitize tumors to chemotherapy and improve patient outcomes. Such approaches exemplify the growing trend of exploiting tumor microenvironment vulnerabilities alongside direct cancer cell targeting.

This study further highlights the importance of the tumor microenvironment, not as a passive backdrop but as an active participant in oncogenesis and therapy resistance. The macrophage-cancer cell axis exemplifies how tumors recruit and manipulate stromal components to survive insults, an insight that is reshaping cancer biology and therapeutic design.

The authors also contextualize their findings within the broader landscape of immunotherapy and targeted treatments, noting that macrophage modulation could synergize with checkpoint inhibitors or other immune-modulatory agents. Fine-tuning the immune landscape may overcome multifactorial resistance mechanisms afflicting breast cancer patients, particularly those with aggressive or refractory disease.

Future research directions suggested by this work include the exploration of macrophage plasticity and the signaling networks enabling phenotype switching. Understanding how macrophages transition from tumor-suppressive to tumor-promoting states could inform temporal targeting strategies, optimizing therapy windows and minimizing resistance development.

Ultimately, this comprehensive investigation into macrophage-cancer cell crosstalk heralds a paradigm shift in breast cancer treatment. It calls for a holistic approach that transcends cancer cells alone, incorporating the intricate cellular milieu that nurtures therapy resistance. By doing so, it sets the stage for revolutionary therapies capable of improving survival rates and quality of life for millions of breast cancer patients worldwide.

The research represents a triumph of interdisciplinary collaboration, integrating immunology, molecular oncology, and translational science. Its findings resonate far beyond breast cancer, hinting at similar resistance mechanisms in other malignancies where macrophages command a crucial role in shaping therapeutic outcomes.

As the fight against breast cancer continues, these insights empower clinicians and scientists alike with novel targets and concepts. By dismantling the protective cocoon formed by macrophages around cancer cells, we edge closer to rendering chemotherapy more effective and durable, transforming the prognosis for a disease that remains a leading cause of cancer mortality among women globally.

Subject of Research:
Breast cancer chemotherapy resistance mediated by macrophage-cancer cell interactions.

Article Title:
Macrophage-cancer cell crosstalk in breast cancer chemotherapy resistance.

Article References:
GUO, A., GU, LH., DING, YY. et al. Macrophage-cancer cell crosstalk in breast cancer chemotherapy resistance. Med Oncol 43, 63 (2026). https://doi.org/10.1007/s12032-025-03161-x

Image Credits: AI Generated

DOI: https://doi.org/10.1007/s12032-025-03161-x

Triple-negative breast cancer, characterized by the absence of estrogen and progesterone receptors and HER2 amplification, has long posed a formidable challenge to oncologists due to its aggressive nature and lack of targeted therapies. Unlike hormone receptor-positive or HER2-positive breast cancers, TNBC does not respond to conventional hormone treatments or HER2-targeted drugs, leaving chemotherapy as the mainstay but often with limited long-term success. Researchers have been intensively studying molecular hallmarks that could serve as Achilles’ heels for this stubborn cancer subtype.

The latest research led by Anna K. Witkiewicz and colleagues sheds light on the retinoblastoma protein—a pivotal tumor suppressor often lost or mutated in various cancers—as a critical factor that influences the fate of TNBC cells under stress. RB functions primarily as a regulator of the cell cycle, preventing uncontrolled cellular proliferation. Its loss has been associated with enhanced tumor progression and resistance to certain treatments. However, this study revealed a paradoxical effect: the absence of RB sensitizes TNBC cells to apoptosis, or programmed cell death, when subjected to cellular stress.

Cellular stress, induced by factors such as DNA damage, oxidative stress, or metabolic strain, typically triggers adaptive responses allowing cells to survive adverse conditions. In cancer, these adaptations can foster resistance to therapies, enabling tumor persistence and relapse. The examination of RB-deficient TNBC models demonstrated that the lack of RB impairs key stress response pathways, making these cancer cells unusually susceptible to apoptosis when challenged with stress-inducing agents.

Using advanced molecular and cellular techniques, the research team meticulously dissected the pathways altered by RB loss. They found that RB-deficient cells failed to effectively engage critical protective mechanisms, including DNA damage repair and reactive oxygen species (ROS) mitigation. This failure culminates in catastrophic cellular damage, tipping the balance towards cell death rather than survival. This insight is pivotal because it implies that therapies designed to induce cellular stress could be particularly effective against TNBC tumors lacking functional RB.

The implications of these findings extend beyond basic science, suggesting a translational strategy to enhance therapeutic efficacy. By combining stress-inducing treatments—such as certain chemotherapeutic drugs or novel agents that elevate cellular oxidative stress—with knowledge of RB status, clinicians could tailor more effective regimens. Specifically, patients with RB-deficient TNBC may benefit from therapies that push cancer cells beyond their stress tolerance limits, triggering apoptosis and reducing tumor burden.

Moreover, this study contributes a compelling rationale for developing diagnostic tools that assess RB functionality in tumors as a biomarker for treatment stratification. Identifying patients whose cancers have lost RB could inform personalized therapy plans, allowing oncologists to exploit this vulnerability with precision. Such an approach aligns perfectly with the burgeoning field of precision oncology, which seeks to match treatments with the genetic and molecular features unique to each patient’s cancer.

Using a combination of in vitro experiments and animal models, the researchers demonstrated that the heightened apoptotic sensitivity observed in RB-deficient TNBC cells translated into substantial tumor regression when subjected to stress-inducing therapies. These preclinical validations underscore the therapeutic potential of this approach and pave the way for clinical trials. The prospect of improving outcomes in a historically difficult-to-treat cancer is particularly thrilling for patients and clinicians alike.

The mechanistic insights uncovered also highlight the broader role of tumor suppressors in modulating the cellular stress response. While RB is traditionally conceptualized as a gatekeeper of cell cycle progression, this study extends its influence to cellular homeostasis pathways that govern survival under duress. Such a dual role may explain why its loss can paradoxically render cancer cells more vulnerable, offering a fresh angle from which to attack tumors.

From a research perspective, this study invites further exploration into the interplay between cell cycle regulators and stress response machinery. How exactly RB interfaces with signaling networks that detect and resolve cellular damage remains an area ripe for investigation. Understanding these molecular crosstalks could uncover additional targets that synergize with RB loss to amplify cancer cell death.

The findings also carry implications for combination therapies. Since RB loss enhances sensitivity to stress-induced apoptosis, integrating stress-inducing agents with immune checkpoint inhibitors or other modalities could unlock synergistic effects. The immune system’s role in clearing apoptotic cells adds another layer of therapeutic potential, where increased tumor cell death may invigorate antitumor immunity.

Critically, the research underscores the importance of cellular context in cancer treatment decisions. Not all TNBC tumors will have RB loss, and this heterogeneity necessitates precise tumor profiling before implementing stress-based therapeutic strategies. Advances in genomic and proteomic technologies can facilitate such detailed characterizations, ensuring tailored interventions that maximize efficacy and minimize side effects.

In summary, this work by Witkiewicz et al. offers a compelling narrative in cancer biology and therapeutics. By unraveling how RB loss primes triple-negative breast cancer cells for apoptosis in response to cellular stress, the study not only identifies a promising vulnerability but also charts a roadmap for clinical exploitation. The intersection of tumor suppressor biology, cellular stress responses, and therapeutic innovation creates an exciting frontier that may soon translate into life-saving treatments for patients grappling with this aggressive cancer subtype.

As breast cancer researchers worldwide grapple with the complexity and resilience of TNBC, these findings inject new optimism into the field. Harnessing the built-in Achilles’ heel created by RB loss and leveraging cellular stress mechanisms could redefine treatment landscapes. Future efforts will undoubtedly focus on validating these insights in clinical settings and expanding our arsenal against one of the deadliest breast cancer variants.

In conclusion, the study represents a beacon of hope illustrating how fundamental molecular discoveries can inspire practical, targeted interventions in cancer care. Exploiting the unique vulnerabilities shaped by genetic aberrations such as RB loss is emblematic of the precision medicine era—transforming daunting clinical challenges into manageable ones. As the scientific community continues to decode cancer’s complexity, such breakthroughs remind us that every genetic quirk in a tumor harbors potential keys to its downfall.

Subject of Research: The role of retinoblastoma protein (RB) loss in sensitizing triple-negative breast cancer to apoptosis induced by cellular stress.

Article Title: RB loss sensitizes triple-negative breast cancer to apoptosis induced by cellular stress.

Article References:
Witkiewicz, A.K., Kaligotla Venkata, S.A., Knudsen, E.S. et al. RB loss sensitizes triple-negative breast cancer to apoptosis induced by cellular stress. Cell Death Discov. 11, 543 (2025). https://doi.org/10.1038/s41420-025-02864-4

Image Credits: AI Generated

DOI: 24 November 2025

In the ever-evolving arena of cancer research, triple-negative breast cancer (TNBC) remains a formidable adversary due to its aggressive nature and limited treatment options. Traditionally elusive in terms of targeted therapies, TNBC’s malignancy is now increasingly understood through the lens of molecular biology and metabolic pathways. A recent comprehensive study spearheaded by Yang, Dong, Wu, and colleagues delves into a critical yet underexplored domain: the intricate involvement of nucleic acid metabolism-related genes (NAMRGs) in shaping TNBC’s pathological characteristics and immune milieu. This investigation, drawing upon transcriptomic analyses of 297 TNBC samples consolidated from three distinct datasets, unravels compelling mechanistic insights with far-reaching clinical implications.

Nucleic acid metabolism, a fundamental cellular process responsible for DNA and RNA synthesis, repair, and degradation, has long been recognized as a pillar supporting tumor proliferation by furnishing requisite biomolecules and energy. However, its specific role in TNBC biology remained inadequately characterized until now. The study harnesses advanced single-cell RNA sequencing alongside rigorous in vitro and in vivo experimentation to establish a nuanced portrait of how NAMRGs modulate tumor metastasis and the complex interactions within the tumor immune microenvironment (TME).

Central to the study is the identification of two discrete molecular subtypes of TNBC marked by distinctive NAMRG expression patterns. These molecular signatures intersect with existing stratification frameworks encompassing four genetic and four pathological subtypes, bridging molecular taxonomy with histopathological contexts. This multidimensional classification not only enriches our understanding of TNBC heterogeneity but also reveals a strong correlation between alterations in nucleic acid metabolism and homologous recombination repair defects (HRD), a key determinant of genomic instability and tumor evolution.

The ramifications of these findings extend to the TME, where altered nucleic acid metabolic activity is associated with shifts in immune cell infiltration profiles. Notably, the TME of tumors exhibiting specific NAMRG expression is characterized by immune exhaustion—particularly within CD8+ T cells—suggesting that nucleic acid metabolism may directly influence immune evasion mechanisms. This revelation positions NAMRGs not merely as passive metabolic players but as active contributors to immune modulation in TNBC, offering fresh therapeutic entry points.

Strikingly, the research introduces a robust prognostic tool, the NAM_model, constructed through the integration of four pivotal NAMRGs—DPYD, PDE6G, PDE8B, and TYMS—along with relevant clinical indicators. This prognostic nomogram reliably differentiates high- and low-risk patient cohorts, with the high-risk group exhibiting markedly poorer outcomes consistent with immune exhaustion phenotypes. Such precision prognostication could transform patient stratification, facilitating personalized treatment regimens tailored to metabolic and immunological tumor profiles.

Among the NAMRGs under scrutiny, PDE8B emerges as a particularly compelling oncogene with no prior association to TNBC metastasis. Experimental evidence from both cellular and animal models confirms PDE8B’s role in promoting tumor growth and facilitating epithelial-mesenchymal transition (EMT), a critical process underpinning metastatic dissemination. This novel link underscores the gene’s potential as both a biomarker and a therapeutic target, expanding the arsenal against TNBC’s metastatic propensity.

Beyond tumor behavior, the study reveals that NAMRG expression correlates significantly with differential sensitivities to chemotherapy and targeted therapeutic agents. This dimension holds immense translational value, indicating that nucleic acid metabolism not only impacts intrinsic tumor biology but may also dictate treatment responsiveness. Consequently, integrating NAMRG profiling into clinical workflows could optimize therapeutic selection and sequencing, elevating chances of treatment success.

Further dissecting the immune landscape, single-cell RNA sequencing offers granular insights into how nucleic acid metabolism intertwines with HRD to shape the phenotype of exhausted CD8+ T cells. The data suggest a feedback mechanism where defective DNA repair pathways exacerbate immune dysfunction, potentially perpetuating an immunosuppressive microenvironment. This interconnectedness highlights the complexity of tumor-immune interactions orchestrated at the metabolic level, advocating for combinatorial approaches leveraging metabolic inhibitors and immunotherapies to overcome resistance.

Importantly, this research embodies a holistic approach by interlinking metabolic pathways, DNA repair mechanisms, tumor heterogeneity, immune landscape, and clinical prognosis. Such integrative analysis transcends conventional single-angle studies, illuminating the multifaceted influence of nucleic acid metabolism in dictating TNBC’s pathobiology and patient outcomes. It invites a paradigm shift in how clinicians and researchers conceptualize cancer progression and therapeutic vulnerabilities.

The implications for immunotherapy are especially profound. Immune exhaustion within the TME has long been a barrier to effective immunomodulation in TNBC, a cancer subtype notoriously refractory to checkpoint inhibitors. Uncovering nucleic acid metabolism as a regulator of immune exhaustion paves the way for novel therapeutic combinations that might reinvigorate anti-tumor immunity and augment responses to immune checkpoint blockade.

This landmark study also challenges researchers to broaden their investigative scope to consider metabolic processes beyond traditional oncogenic signaling pathways. The metabolic state of tumors—particularly nucleic acid turnover—emerges not only as a hallmark of cellular proliferation but as an orchestrator of microenvironmental crosstalk and immune escape. This broadens the canvas for therapeutic interventions targeting metabolism-linked vulnerabilities.

In summarizing their work, Yang et al. emphasize that the integrated analysis of NAMRGs offers a vital bridge from molecular discoveries to clinical application. The ability to link metabolic gene expression profiles with clinical stages, pathological subtypes, immune phenotypes, and patient prognosis underscores the promising future of metabolism-informed oncology. Such breakthroughs herald a new era of precision medicine for TNBC, where insights into nucleic acid metabolism will inform prognosis, guide treatment, and perhaps fundamentally alter disease management.

As scientific inquiry accelerates, the validation of PDE8B and other nucleic acid metabolism-related genes as oncogenic drivers and predictive markers promises to spur drug development targeting these molecules. With further translational research, inhibitors modulating nucleic acid metabolic enzymes could complement existing therapeutic regimens, particularly in reversing immune exhaustion and curtailing metastasis.

Taken together, this comprehensive study unveils the hidden yet pivotal roles of nucleic acid metabolism in TNBC pathogenesis and immunology. It dispels previous uncertainties regarding the metabolic underpinnings of tumor aggressiveness and immune evasion, thereby charting a roadmap toward innovative, metabolism-oriented interventions. For patients grappling with TNBC, which often strikes with brutal intensity and limited treatment options, these findings kindle new hope for improved outcomes and durable remission.

This research not only enriches the current scientific canon but signals a clarion call to the broader cancer research community: to reexamine tumor metabolism as a multifaceted driver of cancer progression and immune landscape sculptor. The time is ripe for metabolism to move from the periphery to the forefront of cancer biology, where it belongs.

Subject of Research: Triple-negative breast cancer, nucleic acid metabolism, tumor microenvironment, immune exhaustion, prognostic modeling

Article Title: Effects of nucleic acid metabolism on prognosis and immune invasion of triple-negative breast cancer

Article References:
Yang, F., Dong, Y., Wu, S. et al. Effects of nucleic acid metabolism on prognosis and immune invasion of triple-negative breast cancer. Genes Immun (2025). https://doi.org/10.1038/s41435-025-00366-y

Image Credits: AI Generated

DOI: 06 November 2025

Breast cancer remains one of the most prevalent malignancies worldwide, and despite advances in systemic therapies, brain metastasis continues to be a formidable clinical challenge. In a groundbreaking review led by Dr. Suling Liu from The First Affiliated Hospital of Zhejiang University, the intricate biological underpinnings and emerging therapeutic avenues of breast cancer brain metastasis (BCBrM) have been comprehensively elucidated. This work sheds light on the evolving landscape where molecular biology converges with translational innovation, underscoring the urgency to develop brain-specific interventions amidst rising incidence rates.

BCBrM affects up to 20% of breast cancer patients, with a predilection for those harboring HER2-positive and triple-negative breast cancer subtypes. Improvements in systemic disease management have paradoxically extended survival, inadvertently increasing the window for brain dissemination. The brain, once considered an immune-privileged sanctuary, is thus emerging as a critical battleground where metastatic breast cancer cells exploit unique neural microenvironmental cues. The clinical reality remains bleak, with limited therapeutic options and dismal outcomes emphasizing the need for refined molecular insights and innovative pharmacological strategies.

At the cellular and molecular scale, metastatic breast cancer cells undergo a dynamic metamorphosis during the metastatic cascade. Initiated by epithelial-mesenchymal transition (EMT), primary tumor cells acquire migratory and invasive capabilities, enabling intravasation into the circulatory system. Once in circulation as circulating tumor cells (CTCs), these cells often enter a dormant state, evading immune detection. This dormancy is a sophisticated survival strategy allowing tumor cells to resist therapeutic assault and adapt to distant niches. Upon arrival in the brain, tumor cells traverse the blood-brain barrier (BBB), a highly selective interface, undergoing mesenchymal-epithelial transition (MET) to reinitiate proliferation, highlighting the plasticity that metastatic cells exploit.

The molecular choreography orchestrating BCBrM involves interlinked signaling pathways including TGF-β, Wnt/β-catenin, PI3K/AKT, Notch, HER2-HER3 heterodimerization, and JAK/STAT cascades. Each pathway plays a pivotal role in regulating cell survival, migration, and immune evasion within the cerebral milieu. Notably, the HER2-HER3 axis, long implicated in breast cancer pathogenesis, emerges as a critical determinant in brain metastatic colonization, potentiating downstream pro-survival signaling. Concurrently, these pathways collaboratively modulate the tumor cells’ ability to remodel the brain microenvironment, fostering a permissive niche that supports metastasis persistence and growth.

The brain microenvironment is a unique and complex ecosystem composed of astrocytes, microglia, neurons, endothelial cells, and pericytes. These resident cells engage in bidirectional communication with metastatic breast cancer cells through molecular conduits such as gap junctions and cytokine networks. Astrocytes, for instance, contribute to metastatic niche formation by secreting cytokines and facilitating metabolic coupling, which in turn enhances tumor cell survival and offers resistance to conventional chemotherapies. Microglia, the brain’s intrinsic immune sentinels, exhibit a dualistic role, capable of both anti-tumor activity and tumor promotion, depending on phenotypic polarization influenced by tumor-derived signals.

Preclinical modeling of BCBrM presents significant challenges but remains indispensable for translational research. Established approaches like intracardiac and orthotopic brain injections in murine models mimic metastatic seeding and progression but cannot fully recapitulate human tumor heterogeneity. Patient-derived xenografts (PDXs) and three-dimensional organoids have emerged as valuable platforms that preserve the genetic and phenotypic complexity of patient tumors while facilitating drug screening. Cutting-edge methodologies involving humanized mouse models, which engraft human immune components, and advanced imaging modalities, are revolutionizing the capacity to study tumor-immune interactions and therapeutic responses within the brain microenvironment.

Therapeutic strategies against BCBrM are rapidly evolving but remain constrained by the formidable blood-brain barrier, which limits drug penetration. Conventional chemotherapies and radiotherapy often yield limited success with significant neurotoxicity. However, novel CNS-penetrant agents represent promising advancements. Small molecule tyrosine kinase inhibitors such as tucatinib and neratinib exhibit enhanced brain bioavailability and target HER2-driven metastatic pathways effectively. Antibody-drug conjugates like trastuzumab deruxtecan combine selective targeting with payload delivery, improving intracranial activity. Moreover, immunotherapeutic approaches harnessing immune checkpoint inhibitors and formulations leveraging nanoparticle-based delivery systems are being intensively investigated to surmount BBB limitations.

Innovations such as focused ultrasound further offer a non-invasive method to transiently disrupt the BBB, thereby facilitating the delivery of therapeutics directly into brain lesions with improved precision and reduced systemic toxicity. These emerging technologies, alongside personalized medicine approaches incorporating genomic profiling, aim to optimize patient-specific treatment regimens. By tailoring therapeutic strategies to the molecular and immunological profiles of individual tumors, there is renewed hope for improving response rates and extending survival.

A vital aspect highlighted in this comprehensive review is the necessity for multidisciplinary collaboration spanning oncology, neuroscience, immunology, pharmacology, and bioengineering. Only through such integrative efforts can robust clinical trial designs be developed, incorporating biomarkers for patient stratification and real-time monitoring of treatment efficacy. The complexity of BCBrM demands a paradigmatic shift from conventional protocols to innovative, adaptable frameworks that encompass novel agents, delivery platforms, and combinatorial therapies.

In summation, breast cancer brain metastasis exemplifies a critical nexus of oncologic and neurologic interplay, marked by cellular plasticity, molecular intricacy, and microenvironmental adaptation. The review by Dr. Liu and colleagues delineates a roadmap that bridges foundational biological mechanisms to therapeutic innovations, illuminating pathways for future research and clinical intervention. As the incidence of BCBrM increases in parallel with improved systemic control, the imperative to translate these insights into effective, brain-directed treatments becomes ever more pressing, promising to transform patient outcomes and quality of life.

Subject of Research: Breast Cancer Brain Metastasis (BCBrM)
Article Title: Breast Cancer Brain Metastasis: Bridging Biological Mechanisms to Therapeutic Innovations
News Publication Date: 24-Oct-2025
Web References: http://dx.doi.org/10.1002/mog2.70043
Image Credits: Suling Liu
Keywords: Breast cancer, brain metastasis, blood-brain barrier, epithelial-mesenchymal transition, HER2, tumor microenvironment, signaling pathways, preclinical models, CNS-penetrant agents, immunotherapy, targeted therapy, nanoparticle delivery, metastasis mechanisms