HOUSTON, DECEMBER 4, 2025 ― At The University of Texas MD Anderson Cancer Center , research breakthroughs are made possible through seamless collaboration between the institution's world-leading clinicians and scientists, bringing discoveries from the lab to the clinic and back. The studies below showcase the latest advances in cancer care, research and prevention.
HER2-targeted therapy shows promising results in rare bile duct cancers
Read the full release | Read the study in JAMA Oncology
Zanidatamab, a bispecific HER2-targeted antibody, delivered clinically meaningful and durable responses for patients with HER2-positive biliary tract cancer (BTC), according to final results from the HERIZON-BTC-01 clinical trial . In this clinical trial, zanidatamab demonstrated an objective response rate of 41.3% and a median duration of response of 15.5 months, while patients whose tumors showed strongest levels of HER2 overexpression experienced even greater benefit – a 51.6% response rate and a median duration of response of 18.1 months Initial trial results were first reported in The Lancet Oncology in June 2023. The trial was led by Shubham Pant, M.D. , professor of Gastrointestinal Medical Oncology and Investigational Cancer Therapeutics .
"The observed objective response rate, prolonged duration of response, and consistent activity in IHC3+ tumors underscores HER2 as a valid therapeutic target in biliary tract cancer and support the emerging role of zanidatamab in the treatment paradigm," Pant said.
Researchers identify target to overcome treatment resistance in preclinical models of KRAS-mutant cancers
Read the full release | Read the study in Nature Cell Biology
Researchers have identified a specific protein, RASH3D19, that is responsible for activation of RAS signaling pathways involved in aggressive tumor growth and resistance to KRAS inhibitors in patients with KRAS-mutant cancers. Blocking RASH3D19 in combination with KRAS inhibitors improved outcomes in preclinical models, suggesting this combination as a potential therapeutic strategy for patients with KRAS-mutant cancers. The study was led by Subrata Sen, Ph.D. , deputy chair of Translational Molecular Pathology , and Hiroshi Katayama, Ph.D., associate professor of Translational Molecular Pathology, along with co-first authors, Warapen Treekitkarnmongkol, Ph.D., and Deivendran Sankaran, Ph.D.
"These findings provide crucial clarity on the mechanisms of RAS pathway activation, identify an actionable target responsible for aggressive disease in patients with KRAS-mutant cancers, and provide insights into the development of resistance to KRAS-targeting drugs. This has significant clinical implications that can, hopefully, improve outcomes for patients," Sen said.
DNA shape and rigidity regulate key players of gene expression
Read the full release | Read the study in Molecular Cell
Researchers have shown that DNA inflexibility, or rigidity, inside the nucleosome regulates the positioning of INO80. This highlights that the physical structure and shape of DNA, not just genetic information, are key components of DNA transcription. It also suggests that the Arp5 subunits may act as sensors that regulate INO80 remodeling depending on the shape of the DNA. The study was co-led by Blaine Bartholomew, Ph.D. , professor of Epigenetics and Molecular Carcinogenesis , and colleagues.
"We have found the remarkable specificity of INO80 to position nucleosomes, the building blocks of chromatin and chromosomes, is due to being stopped by highly inflexible DNA. By taking snapshots during remodeling, we were able to identify the steps in nucleosome movement blocked by these specific regions in the genome," Bartholomew said.
Study identifies target for disease hyper progression after immunotherapy in kidney cancer
Read the full release | Read the study in Nature Communications
Researchers discovered that renal medullary carcinoma (RMC) cells use an adaptive mechanism called "myeloid mimicry" to hide from the immune system and promote disease hyper progression after immunotherapy , highlighting specific targets that overcome treatment resistance in preclinical models. The study was led by Pavlos Msaouel, M.D., Ph.D. , and Giannicola Genovese, M.D., Ph.D. , both associate professors of Genitourinary Medical Oncology; Jianjun Gao, M.D., Ph.D. , professor of Genitourinary Medical Oncology; and Linghua Wang, M.D., Ph.D. , associate professor of Genomic Medicine, associate member of the James P. Allison Institute™ and focus area co-lead for the Institute for Data Science in Oncology .
"We identified a myeloid mimicry pathway that can drive tumor hyper progression following immunotherapy in renal medullary carcinoma. Inhibiting this pathway may offer a promising strategy to advance into clinical studies," Msaouel said.
Study provides comprehensive insights into DNA language models
Read the full release | Read the study in Nature Communications
Researchers have performed a comprehensive evaluation of five artificial intelligence (AI) models trained on genomic sequences, known as DNA language models. These comparisons provide valuable insights into their strengths and weaknesses and offer a framework for selecting appropriate models based on specific genomic tasks. The study was led by Chong Wu, Ph.D ., assistant professor of Biostatistics and affiliate of the Institute for Data Science in Oncology ; and Peng Wei, Ph.D. , professor of Biostatistics.
"Our benchmarking study demonstrates that choices, such as pre-training data, sequence length and how we summarize model embeddings, can shift performance as much as changing the DNA language model itself. This kind of rigorous benchmarking is critical to ensure DNA language models are used in a transparent, reproducible way as they move closer to supporting clinical decision-making," Wu said.
