Memorial Sloan Kettering Cancer Center researchers have reported a series of findings that could reshape treatment strategies across oncology, from drug-resistant leukemia and bone metastasis to smoking cessation, kidney disease, insurance policy, and epilepsy surgery. The studies reveal how cancer cells adapt genetically and physically, how remote care can improve outcomes, and how detailed molecular maps may guide the next generation of medicines.
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
