The University of Texas MD Anderson Cancer Center continues to push the boundaries of cancer research with a series of groundbreaking studies, spotlighted in its August 7, 2025 Research Highlights. These developments span novel therapeutic targets, innovative diagnostic approaches, and new insights into treatment resistance across multiple cancer types, including lung, pancreatic, ovarian, and breast cancers, as well as myelodysplastic syndromes (MDS).
At the forefront is the identification of NSD2, a protein whose elevated activity fuels growth in notoriously difficult-to-treat cancers harboring KRAS mutations. KRAS-mutated lung and pancreatic carcinomas have long posed significant therapeutic challenges due to their aggressive behavior and resistance to conventional treatments. Led by Dr. Pawel Mazur, a multi-institutional study has unveiled a new pharmacologic agent capable of targeting NSD2 directly. This drug reprograms chromatin architecture, thereby reversing oncogenic transcriptional programs. Preclinical models demonstrated not only the prevention of tumor progression but also improved survival outcomes when the drug was used independently. Remarkably, combining this NSD2 inhibitor with the KRAS-targeting agent sotorasib induced tumor regression and, in some cases, complete tumor eradication, providing a compelling rationale for clinical translation.
In a separate arena of cancer supportive care, researchers are focusing on the debilitating syndrome of cancer-associated cachexia, characterized by rapid weight loss and muscle wasting. This condition, implicated in approximately one-third of cancer mortality, remains largely untreatable. Dr. Xiling Shen and colleagues have pinpointed the brain-liver axis, specifically the neuroinflammatory disruption of the vagus nerve, as a critical mediator of cachexia. Their investigations revealed that elevated levels of the chemokine CCL2 during cancer progression compromise vagal signaling, impairing liver metabolic functions crucial for maintaining muscle and weight homeostasis. The team explores the novel utilization of non-invasive electronic wearables designed to modulate this neuroinflammatory pathway, offering a promising avenue to mitigate or delay cachexia onset.
Addressing symptomatic management in advanced cancer, the therapeutic efficacy of lorazepam has been revisited in patients experiencing agitated delirium. Dr. David Hui’s NIH-funded Phase II study conducted rigorous patient trials comparing lorazepam, haloperidol, their combination, and placebo interventions. Findings demonstrate that lorazepam alone or combined with haloperidol significantly diminishes agitation levels, outperforming haloperidol monotherapy. This reduces the need for breakthrough dosing and potentially improves quality of life, marking a pivotal shift in delirium management protocols.
Simultaneously, precision oncology advances through machine learning are poised to transform therapeutic decisions in metastatic non-small cell lung cancer (NSCLC). The challenge of selecting between immune checkpoint inhibitor monotherapy or combination chemotherapy has been addressed by Dr. Jia Wu’s team, who developed A-STEP—a sophisticated predictive model incorporating 34 clinical and biological variables from over 2,300 patient cases across multiple centers. This model successfully assessed individual benefit likelihood for combination therapy, recommending treatment alterations in more than half of patients within an external validation cohort. Patients receiving model-informed therapies exhibited notably improved progression-free survival after two years, highlighting the transformative impact of artificial intelligence on oncologic treatment personalization.
Resistance mechanisms remain a formidable barrier in targeting KRAS-driven tumors, with many cancers rapidly developing tolerance to KRAS inhibitors. A study led by Drs. Wantong Yao, Scott Kopetz, and Haoqiang Ying uncovered the pivotal role of the cell surface protein SDC1 in fostering this resistance. Initially downregulated upon therapy, SDC1 expression resurged in resistant pancreatic and colorectal tumors. The oncogene YAP1 was identified as a master regulator within this axis, reactivating SDC1 and downstream receptor tyrosine kinase signaling pathways that drive tumor survival despite KRAS blockade. These insights not only illuminate a fundamental resistance pathway but suggest that targeting the YAP1-SDC1 signaling nexus could potentiate the efficacy and durability of KRAS inhibitors. Furthermore, SDC1 is proposed as a novel biomarker to monitor treatment response and relapse.
For patients battling advanced ovarian cancer, minimal residual disease (MRD) poses a silent but significant threat, often eluding detection despite aggressive frontline therapies. Led by Dr. Amir Jazaeri, investigations utilizing second-look laparoscopy combined with circulating tumor DNA assays revealed that 42.1% of patients harbored residual disease post-treatment. The presence of MRD correlated strongly with poorer progression-free survival. Employing cutting-edge spatial multi-omics, researchers dissected the cellular and molecular architecture of these MRD lesions, identifying critical signaling pathways and potential therapeutic targets. These findings pave the way for more refined, individualized therapeutic strategies aimed at eradicating MRD and enhancing long-term survival in ovarian cancer patients.
Within the realm of hematologic malignancies, myelodysplastic syndromes (MDS) continue to reveal complex biological subtypes with distinct clinical behaviors. The erythroid predominance (EP) subtype, characterized by a high proportion of red blood cell precursors in bone marrow, displays unique genetic signatures, notably a high prevalence of TP53 mutations. Under the guidance of Dr. Guillermo Montalban Bravo, an analysis of 371 MDS patients revealed that EP MDS exhibited aggressive disease features, inferior responses to venetoclax-based therapies, and poorer overall survival. This resistance is hypothesized to stem from elevated BCL-XL protein levels, suggesting a need for novel therapeutic strategies targeting this anti-apoptotic molecule. Three genetically defined subgroups within EP MDS with distinct prognostic outcomes were also delineated, underscoring the heterogeneity and necessity for tailored treatment approaches in this patient population.
Breast cancer research at MD Anderson has also made significant strides in understanding and combating resistance mechanisms. In hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer, CDK4/6 inhibitors have substantially improved outcomes, yet resistance remains a clinical hurdle. Dr. Khandan Keyomarsi’s team revealed that inflammatory signaling driven by elevated interleukin-6 (IL-6) activates STAT3, a transcription factor facilitating tumor progression and drug resistance. Importantly, IL-6 levels can be monitored non-invasively via blood assays, offering a predictive biomarker to identify patients at risk of resistance early. The group further demonstrated that inhibiting the STAT3 pathway in preclinical resistant tumor models suppresses cancer growth, highlighting a promising therapeutic avenue to overcome resistance and improve patient prognosis.
Beyond these scientific advances, MD Anderson Cancer Center recently earned the Advanced Inpatient Diabetes Certification from The Joint Commission, recognizing its excellence in managing diabetes within the inpatient setting. This achievement reflects the institution’s commitment to comprehensive, multidisciplinary patient care extending beyond oncology.
Collectively, these research efforts emphasize the critical importance of interdisciplinary collaboration, integrating molecular biology, immunology, neurology, and computational sciences to accelerate development of novel diagnostics and therapies. The insights gained at MD Anderson not only deepen understanding of cancer biology but also hold transformative potential to improve survival rates and quality of life for patients worldwide. As oncologic paradigms continue to evolve, the center’s commitment to translating laboratory discoveries into clinical innovations remains steadfast, with promising therapies on the horizon for some of the most intractable cancers.
Subject of Research: Cancer research focusing on novel therapeutic targets, treatment resistance mechanisms, diagnostic innovations, and supportive care advancements across lung, pancreatic, ovarian, breast cancers, and myelodysplastic syndromes.
Article Title: MD Anderson Cancer Center Unveils Multidimensional Advances in Cancer Therapeutics and Diagnostics
News Publication Date: August 7, 2025
Web References:
- https://www.mdanderson.org/newsroom/research-highlights.html
- https://www.nature.com/articles/s41586-025-09299-y
- https://www.cell.com/cell/fulltext/S0092-8674(25)00805-0
- https://jamanetwork.com/journals/jamaoncology/fullarticle/2837082
- https://www.nature.com/articles/s41467-025-61823-w#Sec7
- https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00326-X
- https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-25-0512/763902/Surgical-and-blood-based-minimal-residual-disease
- https://www.nature.com/articles/s41375-025-02711-6
- https://www.nature.com/articles/s41698-025-01041-1
References: See respective journal articles linked above.
Keywords: Cancer research, KRAS mutations, NSD2 inhibitor, cachexia, vagus nerve, lorazepam, delirium, machine learning, non-small cell lung cancer, treatment resistance, SDC1, YAP1, minimal residual disease, ovarian cancer, myelodysplastic syndromes, erythroid predominance, TP53 mutation, venetoclax resistance, CDK4/6 inhibitor resistance, IL-6, STAT3, breast cancer, cancer immunology, precision oncology.
