MD Anderson Unveils Wave of Cancer Breakthroughs From Lung Immunotherapy to Microbiome Medicine

Researchers at The University of Texas MD Anderson Cancer Center have unveiled a sweeping collection of new findings that span the full arc of modern oncology, from a Phase 3 immunotherapy success in advanced lung cancer to blood tests that could spare patients unnecessary chemotherapy. The studies, several of which are being presented at the 2026 American Society for Radiation Oncology Annual Meeting from September 26 to 30, illustrate the institution’s strategy of moving discoveries between laboratory and clinic in both directions. Together, they touch on some of the most consequential questions in cancer medicine today: how to overcome drug resistance, how to predict who will benefit from engineered immune cells, how to identify which patients can safely skip toxic treatments, and how to manage the side effects that accompany the most powerful immunotherapies.

Perhaps the most clinically immediate result comes from the global Phase 3 HARMONi trial, published in The Lancet Oncology, which tested a novel bispecific immunotherapy called ivonescimab in patients with EGFR-mutant non-small cell lung cancer. Patients who received ivonescimab plus chemotherapy were 48 percent less likely to experience cancer progression or death than those receiving chemotherapy alone. Those on the combination lived a median of 6.8 months without their disease worsening, compared with 4.4 months for chemotherapy alone, and the treatment also improved tumor responses while maintaining a manageable safety profile. The result matters because EGFR-targeted therapies, despite their transformative impact, eventually stop working in nearly every patient. “Despite major advances in EGFR-targeted therapies, resistance remains inevitable for most patients, and treatment options after progression are limited,” said trial co-lead Xiuning Le, M.D., Ph.D., associate professor of Thoracic/Head and Neck Medical Oncology. “These results show that adding ivonescimab to chemotherapy can extend disease control and may offer an important new option for these patients.”

A second study, published in Cancer Discovery, reveals a previously unknown way that prostate tumors defend themselves against the immune system. Led by Di Zhao, Ph.D., associate professor of Experimental Radiation Oncology, and Nicholas Navin, Ph.D., chair of Systems Biology, the research showed that the immune checkpoint molecule B7-H3 plays a dual role in castration-resistant prostate cancer. Rather than simply dampening immune activity, B7-H3 also reshapes the tumor microenvironment, reprogramming the cells surrounding a tumor so that cancer can grow and resist treatment. The team found that combining a B7-H3-targeted therapy with MEK inhibition improved antitumor responses and prolonged survival in preclinical models. The discovery may also explain why therapies aimed solely at blocking B7-H3 have shown limited efficacy in trials: the molecule functions as a backup physical defense for the tumor, so attacking it alone leaves the reshaped microenvironment intact. “By uncovering how this process works, we identified a promising strategy that combines B7-H3-targeted therapy with MEK inhibition,” Zhao said, adding that the findings could guide more personalized treatments for patients whose tumors are unlikely to respond to B7-H3 therapy by itself.

Off-the-shelf CAR T cell therapies, which use donor-derived immune cells engineered to attack cancer, promise to make this powerful treatment far more accessible than patient-specific products. But outcomes vary dramatically from one patient to the next, and a new study in Cancer Discovery helps explain why. Researchers led by corresponding author Pavan Bachireddy, M.D., assistant professor of Hematopoietic Biology and Malignancy and scientific director of the ECLIPSE platform, traced how these cells behave inside patients. They found that some patients’ immune systems may reject the donor-derived CAR T cells before the cells can fully expand and eliminate cancer, and they identified specific CAR T cell populations that appear better equipped to multiply, persist, and destroy malignant cells. “One of the biggest questions in the field has been why the same off-the-shelf CAR T cell therapy can lead to dramatically different results in different patients,” Bachireddy said. By identifying both patient-side and product-side characteristics that influence response, the work points toward engineering better cells and selecting the patients most likely to benefit.

In a finding with immediate implications for surgical oncology, the largest study to date of localized appendix cancer suggests that most patients may be able to safely avoid chemotherapy after surgery. Published in JAMA Surgery and led by John Paul Shen, M.D., associate professor of Gastrointestinal Medical Oncology, together with research fellow Sacha El Khoury, M.D., the analysis found that fewer than 10 percent of patients experienced recurrence after surgery. Chemotherapy given after surgery was not associated with improved survival or a lower risk of relapse, even among patients considered higher risk. The team also identified specific tumor characteristics and genomic alterations that may help doctors predict which patients are most likely to see their cancer return. “For too long, the outdated notion that appendix cancer behaves similarly to colon cancer has driven treatment decisions for our patients,” Shen said. “Our findings demonstrate that appendix cancer has a distinct biology and that, for most patients with localized disease, the risk of relapse is low.” The results could spare thousands of patients the toxicity of treatment that appears to offer little benefit.

Medullary thyroid cancer has long puzzled physicians because its bone metastases look unlike those of almost any other cancer, producing abnormal accumulations of bone rather than the destructive lesions typical of skeletal disease. A study published in Cell Reports Medicine, led by Theresa Guise, M.D., professor of Endocrine Neoplasia and Hormonal Disorders, offers a mechanistic explanation and a practical monitoring tool. The researchers discovered that cancer cells carrying RET mutations produce elevated levels of a protein called osteoprotegerin, or OPG, which disrupts the normal balance of bone renewal by blocking bone destruction and favoring bone formation. “RET-mutant cancer cells may send signals that encourage new bone formation while stopping the breakdown of old bones, causing a pile-up,” Guise said. This imbalance could account for the unusual bone lesions seen uniquely in medullary thyroid cancer, and it suggests that measuring OPG levels through a simple blood test could identify and track patients who develop bone metastases, potentially catching aggressive disease earlier than imaging alone.

Two separate studies tackle the darker side of immunotherapy: the inflammatory side effects that can force patients to stop treatment. In a Phase 1/2 trial published in Cell Reports Medicine, fecal microbiota transplantation, or FMT, showed striking results against immunotherapy-related colitis, a painful inflammation of the colon. Nearly 77 percent of the first 13 patients treated with FMT saw improvements, with symptoms subsiding in a median of just 1.5 days, and eight of the 10 patients who responded remained in remission during follow-up. The approach could allow patients to avoid steroids and other immune-suppressing drugs. “What stands out in these results is the quick onset of clinical improvement from an early introduction of microbiome therapy as well as the number of patients who were able to resume cancer treatment,” said principal investigator Yinghong Wang, M.D., Ph.D., professor of Gastroenterology & Hepatology. Complementing that work, a study in Cell Reports led by Roza Nurieva, Ph.D., professor of Immunology, identified a previously unknown role for B cells in triggering and sustaining checkpoint inhibitor colitis. Changes in circulating B cell activity appeared before symptoms emerged, suggesting a blood-based biomarker that could flag at-risk patients early. “Early B cell dysregulation sets off an inflammatory cascade in some patients while they are asymptomatic,” Nurieva said, describing it as both a driver and a predictive biomarker that could guide preventive strategies.

Prediction also drove a team working on pneumonitis, a potentially life-threatening lung inflammation that affects roughly 10 percent of lung cancer patients receiving immunotherapy and is notoriously difficult to anticipate. Researchers led by Jia Wu, Ph.D., associate professor of Imaging Physics, with co-senior authors Ajay Sheshadri, M.D., and Mehmet Altan, M.D., developed an artificial intelligence model that analyzes routine chest CT scans obtained before treatment begins. The model identified imaging patterns associated with future pneumonitis risk, outperforming current approaches that rely on subjective image review and clinical risk factors that fail to capture underlying vulnerability. “Pneumonitis remains one of the most challenging complications of immunotherapy because it can be difficult to predict before symptoms appear,” Wu said. “Our model was able to identify signals associated with future risk using information that already exists in routine CT scans.”

Taken together, the nine studies sketch a future in which cancer care is increasingly individualized at every stage: choosing the right immunotherapy combination for resistant lung tumors, pairing checkpoint blockade with pathway inhibition in prostate cancer, screening patients before CAR T infusion, sparing appendix cancer patients unnecessary chemotherapy, tracking bone metastases with a blood protein, and predicting or preempting the immune complications of treatment itself. The common thread is the integration of genomic, cellular, imaging, and microbiome data into decisions that were once made by broad tumor categories alone. As these findings move from preclinical models and early trials toward routine practice, they reinforce the central premise behind MD Anderson’s collaborative model, that discoveries made in the laboratory reach patients faster when clinicians and scientists work as a single, continuous enterprise.

Subject of Research: Recent cancer research advances at MD Anderson in immunotherapy, CAR T cell therapy, surgical oncology, and treatment side effect prediction

Article Title: UT MD Anderson shares latest research breakthroughs

Article References: UT MD Anderson shares latest research breakthroughs. (n.d.). Original publication

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Keywords: MD Anderson, cancer research, immunotherapy, ivonescimab, EGFR-mutant lung cancer, B7-H3, prostate cancer, CAR T cell therapy, appendix cancer, medullary thyroid cancer, fecal microbiota transplantation, pneumonitis