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The European Society for Medical Oncology (ESMO) Congress brings together international experts for collaborative discussions on every area of oncology research, from diagnosis and treatment to survivorship.

As the chair of the ESMO Congress 2025 Developmental Therapeutics track, I¡¯m excited about the many significant studies that MD Anderson researchers are presenting at this year¡¯s meeting. Here are five notable presentations that showcase our application of advanced precision oncology.

1. Leveraging molecular profiling to decipher the genetic landscapes of rare cancers

Rare cancers remain understudied despite making up around a quarter of new cancer diagnoses annually. One reason is a lack of biological samples, in part because of the small, geographically dispersed patient populations for each type of rare cancer.

To address this problem, MD Anderson¡¯s Rare Tumor Initiative collected tissue samples from over 1100 patients with rare cancers. , associate professor of Genomic Medicine, will present analysis results from the molecular profiling of this collection, which is the largest contemporary cohort of molecularly profiled rare cancers.

Molecular profiling is vital for rare cancers because it provides precise diagnoses and helps identify genetic changes that drive tumor growth. This genetic blueprint aids in the development of targeted therapies and enables ¡°tumor-agnostic¡± clinical trials based on mutations rather than cancer type, avoiding many of the limitations of a small patient population. It also uncovers inherited risks, giving families important health insights and highlighting the value of rare cancer research for everyone.

2. Evaluating an established antibody-drug conjugate for HER2 positive colorectal cancer

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate originally developed for the treatment of HER2 positive breast cancer. T-DXd combines trastuzumab, a monoclonal antibody that acts as a homing device, with deruxtecan, a topoisomerase I inhibitor. It uses the trastuzumab to find HER2 positive cancer cells. Once attached, the deruxtecan is released inside the cancer cell. Its unique "bystander effect" allows it to also kill surrounding cancer cells, even those with low HER2 expression.

DESTINY-CRC02, a Phase II trial led by , professor of Gastrointestinal Medical Oncology, evaluates the safety and efficacy of T-DXd in patients with pretreated HER2 positive colorectal cancer.

Raghav will present final analysis results, which show that T-DXd is a critical new treatment option for patients with this hard-to-treat type of colorectal cancer, including those with RAS mutations. T-DXd provides a more targeted, potentially more tolerable therapy, translating to renewed hope and a better quality of life for patients.

3. HIF inhibitor for treatment of rare neuroendocrine tumors

Belzutifan was the first hypoxia-inducible factor-2 alpha (HIF-2¦Á) inhibitor to be approved by the Food and Drug Administration (FDA). It works by blocking the overactive HIF-2¦Á sensor. By shutting off this sensor, the drug stops cancer cells from growing and dividing constantly, which slows down tumor growth and may even shrink tumors.

Most metastatic pheochromocytomas or paragangliomas (PPGL) ¡ª two rare types of neuroendocrine tumors ¡ª have dysregulation of the HIF-2¦Á pathways. , professor of Endocrine Neoplasia and Hormonal Disorders, will share results from the Phase II LITESPARK-015 trial, which evaluated the use of belzutifan for patients with PPGL.

Results from this trial led to the FDA approval of belzutifan for patients with PPGL, which represents a major step forward in this rare disease. Belzutifan offers a new and more targeted oral treatment option with a better side-effect profile than older therapies, including fewer blood pressure issues.

4. Second-line therapy outcomes of patients with chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a type of cancer that starts in the bone marrow. Patients with CML often develop resistance to or intolerance of their initial (first-line) treatment, leading to second-line treatment. However, comprehensive data on second-line therapy outcomes is lacking.

, assistant professor of Leukemia, will present data from a retrospective analysis of second-line treatment outcomes of patients with CML.

Studying second-line therapy outcomes helps identify and understand reasons for first-line failure. Haddad¡¯s results suggest that reducing the first-line dose of tyrosine kinase inhibitors may reduce the risk of intolerance that leads to the switching of therapies. In general, analyses like these can help us refine initial treatment strategies and selection based on a patient's profile.

5. First-in-class treatment for refractory mesothelioma

Finally, I will be presenting results from a Phase I/II trial assessing the first-in-class drug VT3989. VT3989 is the first drug to effectively target and inhibit the YAP-TEAD signaling pathway, previously considered an undruggable pathway.

This pathway is frequently disrupted in many cancers, allowing tumor cells to grow and spread unchecked. Imagine cancer cells with a faulty ¡°gas pedal¡± that is stuck down, causing the cells to grow out of control. By blocking the TEAD protein, VT3989 stops the cancer-promoting interaction with the YAP protein, effectively acting as a ¡°brake¡± on tumor growth.

Early trial results are promising, particularly for advanced mesothelioma patients for whom other therapies have failed, showing durable tumor shrinkage and disease stability. VT3989¡¯s unique mechanism of action and these encouraging early clinical results led to orphan drug designation from the FDA, highlighting the critical need this therapy addresses.

MD Anderson at ESMO

These studies demonstrate the power of scientific innovation and precision medicine to address long-standing challenges in cancer care, especially for patients with limited options. They exemplify MD Anderson's mission to end cancer by integrating patient care and research, and I¡¯m looking forward to seeing these advancements drive us towards more precise, data-driven oncology.

, is the Ransom Horne Jr. Endowed Professor for Cancer Research, Vice President and Head of Clinical Development, Therapeutics Discovery at MD Anderson.