MD Anderson Research Highlights for August 7, 2025
- Promising targets for lung and pancreatic cancers
- Electronic wearables for cancer-associated weight and muscle loss
- Insights into KRAS-mutated cancers, NSCLC, ovarian cancer and MDS
- A new therapeutic strategy for HR+/HER2- breast cancer
HOUSTON, AUGUST 7, 2025 ― The University of Texas MD Anderson Cancer Center’s Research Highlights showcases the latest breakthroughs in cancer care, research and prevention. These advances are made possible through seamless collaboration between MD Anderson’s world-leading clinicians and scientists, bringing discoveries from the lab to the clinic and back.
Novel drug confirms NSD2 protein as therapeutic target in lung and pancreatic cancers
Read summary | Read in Nature
Studies have shown that the NSD2 protein fuels cancer growth, particularly in difficult-to-treat cancers with KRAS mutations, suggesting it has potential as a therapeutic target. A new multi-institutional study led by Pawel Mazur, Ph.D., confirmed that NSD2 can be targeted with a new drug. Blocking NSD2 effectively reprogrammed the DNA structure, which reversed and prevented new cancer growth in preclinical models of KRAS-mutant lung and pancreatic cancers. The NSD2 inhibitor alone improved survival and, when combined with the KRAS inhibitor sotorasib, resulted in tumor regression and complete elimination. These results provide insights into NSD2’s role in driving cancers and support further evaluation of the novel NSD2 inhibitor drug used in this study. Formerly known as IACS-17817, the new drug was developed in collaboration between Mazur’s lab and the Therapeutics Discovery division at MD Anderson.
Targeting brain-liver pathway with electronic wearables could prevent cancer-associated weight and muscle loss
Read summary | Read in Cell
Many patients with cancer develop a serious and currently incurable condition called cachexia, which is characterized by rapid weight and muscle loss and is responsible for nearly one-third of cancer-related deaths. Cachexia is driven in part by inflammation affecting the parasympathetic nervous system and liver function. Since the vagus nerve regulates the parasympathetic nervous system, Xiling Shen, Ph.D., and colleagues examined its role in cancer-associated cachexia. Preclinical models and patient blood samples showed that cancer progression triggers inflammation, significantly elevating levels of the CCL2 protein, disrupting communication along the vagus nerve and leading to lower levels of a key liver function regulator. The findings suggest that targeting this neuroinflammatory pathway by non-invasive, electronic wearables is a potential therapeutic strategy to prevent or delay the onset of cancer-associated cachexia.
Lorazepam significantly reduces agitation in patients with advanced cancer and delirium
Read summary | Read in JAMA Oncology
Many patients with advanced cancer are significantly impacted by agitated delirium, but there are conflicting results on treating this condition with medication. To provide insights, David Hui, M.D., and colleagues examined the effects of different medications on treating delirium in 111 patients with advanced cancers. The researchers examined patient responses to haloperidol and lorazepam – both separately and combined – compared to a placebo, with patients receiving scheduled doses every four hours. Early results from the NIH-funded Phase II trial were presented at the 2024 European Society for Medical Oncology (ESMO) Congress. Follow-up results show that lorazepam, alone or with haloperidol, significantly reduced agitation more than haloperidol alone or a placebo. Patients treated with lorazepam separately or in combination with haloperidol also required fewer extra doses to calm breakthrough agitation. These findings suggest that lorazepam may be a more effective option for managing agitation in patients with advanced cancer.
Machine learning model improves treatment selection in non-small cell lung cancer
Read summary | Read in Nature Communications
A significant challenge in developing treatment plans for patients with metastatic non-small cell lung cancer (NSCLC) is deciding whether to use immune checkpoint inhibitors alone or in combination with chemotherapy. Monotherapy is effective for many patients and is associated with fewer adverse effects. However, for patients who do not respond, the crucial time lost could lead to tumor progression. Unfortunately, there is a lack of reliable data to guide clinicians in this area. A team led by Jia Wu, Ph.D., used over 2,300 cases from four different cancer centers to develop a machine learning model called A-STEP (Attention-based Scoring for Treatment Effect Prediction) that employs 34 different variables to calculate an individual’s potential benefit from combination therapy. In a simulation on an external data set, the model recommended treatment changes in more than half of the patients, and those treated with its recommendation showed improved progression-free survival after two years. While this specific use needs continued validation, this study demonstrates the potential of this approach to inform complex clinical decisions.
Researchers identify new approach to overcome resistance to KRAS-targeted therapies
Read summary | Read in Cell Reports Medicine
Many cancers with KRAS mutations, the most commonly mutated oncogene, develop rapid resistance to targeted therapy with KRAS inhibitors. A recent study by Wantong Yao, M.D., Ph.D., Scott Kopetz, M.D., Ph.D., and Haoqiang Ying, M.D. Ph.D., and colleagues discovered that SDC1, a cell surface protein involved downstream of the KRAS-mutated pathway and associated with pancreatic cancer progression, plays a critical role in acquired resistance to KRAS inhibitors. In preclinical models of KRAS-mutant pancreatic and colorectal cancers, SDC1 expression on the cell surface initially declined following KRAS inhibition but later re-emerged in resistant tumors. Mechanistic analyses uncovered the YAP1 oncogene as a major coordinator of SDC1 cell surface reactivation that further mediates the activation of multiple receptor tyrosine kinases and drives the development of KRAS inhibitor resistance. These findings highlight the YAP1-SDC1 axis as a key mechanism underlying this resistance and point to promising potential therapeutic vulnerability to enhance the durability of KRAS-targeted therapies. Further, the researchers suggest SDC1 may be a useful biomarker for monitoring relapse following KRAS inhibitor treatment.
Study provides insights into advanced ovarian cancer tumors after treatment
Read summary | Read in Clinical Cancer Research
Many patients with advanced ovarian cancer treated with frontline therapies still end up with clinically undetectable amounts of cancer cells afterward, called minimal residual disease (MRD), leading to high likelihood of recurrence. However, there are no reliable tests to detect MRD, and its biological features remain understudied. Residual cancer cells escape the effects of surgery and chemotherapy and are the reason why cure rates for advanced ovarian cancer have remained low for many decades. To provide insights, researchers led by Amir Jazaeri, M.D., examined the detection rates and prognostic value of methods via minimally invasive, second-look laparoscopy and circulating tumor DNA (ctDNA) in 95 patients with high-grade epithelial ovarian cancer. Forty of 95 patients (42.1%) had surgically detected MRD, which was associated with poorer progression-free survival. The researchers used spatial multi-omics to characterize these lesions, providing insights into signaling pathways and identifying potential targets in MRD tumors to guide personalized treatments for patients with advanced ovarian cancer.
MDS subtype associated with poor outcomes after venetoclax-based therapy
Read summary | Read in Leukemia
Myelodysplastic syndromes (MDS) are a group of diseases in which the bone marrow does not produce enough healthy blood cells. The erythroid predominance (EP) subtype, marked by 50% or more erythroid cells (red blood cell precursors) in the bone marrow, has distinct biology, prognoses and drug sensitivities. To study this, researchers led by Guillermo Montalban Bravo, M.D., evaluated an MDS cohort of 371 patients, 18% of whom had EP MDS. They discovered EP MDS has unique genetic patterns and a high frequency of mutations in the TP53 gene. EP MDS was associated with more aggressive disease, inferior responses and poor survival rates after treatment with the BCL2 inhibitor venetoclax. The results indicate that venetoclax resistance may be associated with higher levels of the BCL-XL protein. The researchers characterized three genetic subgroups within EP MDS, each with different survival outcomes. These findings suggest that monitoring bone marrow erythroid cells can benefit patients with MDS and highlight the need for treatments targeting BCL-XL in these patients. Learn more in Leukemia.
New biomarker and strategy identify and overcome resistance in HR+/HER2- breast cancer
Read summary | Read in NPJ Precision Oncology
CDK4/6 inhibitors are targeted therapies commonly used as first-line treatments for patients with hormone receptor-positive HER2-negative (HR+/HER2-) metastatic breast cancer. However, some patients stop responding to CDK4/6 inhibitors, and the mechanisms behind this acquired resistance are poorly understood. In a new study led by Khandan Keyomarsi, Ph.D., researchers discovered that the inflammatory protein IL-6 becomes elevated in these patients, which then triggers another protein – STAT3 – that helps tumors progress. This highlights the potential of monitoring IL-6 levels, which are easily measured in blood samples, as an early predictive biomarker for CDK4/6 inhibitor resistance, allowing physicians to guide patients toward more effective treatments. Further, the researchers also demonstrated that blocking the pathway using a STAT3 inhibitor stopped or slowed tumor growth in preclinical models of resistant cancer.
Honors and Awards
- MD Anderson has been recognized for demonstrating excellence in providing care for patients with diabetes, earning Advanced Inpatient Diabetes Certification by The Joint Commission
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