Breakthrough Discoveries

CROSSROADS: CROSS-tissue RegeneratiOn Aberrancy Drives Systemic precancer escape

Team Leaders: Simona Colla, Ph.D., and Andrea Viale, Ph.D.

Current biomarkers detect mutations and precancerous lesions but often fail to predict which cells will progress to cancer. Through the integration of basic and translational research, this project will define the fundamental biology of precancer cell states and what’s known as somatic mosaicism, when mutations cause genetically distinct populations of cells to coexist within the same individual. CROSSROADS will define precancer progression as a coordinated, systemic evolutionary process rather than a collection of isolated, tissue-specific events.

Dual specificity CAR T cells for SCLC and other rare neuroendocrine carcinomas

Team Leaders: Lauren Byers, M.D., and Carl Gay, M.D., Ph.D.

This project aims to launch a new cell therapy, OBT-601, as a potential new treatment for small cell lung cancer (SCLC). In parallel, it also aims to develop a pre-clinical package to support the efficacy of this therapeutic agent beyond SCLC, potentially making way for a new treatment option for patients with other rare, often neglected high-grade neuroendocrine carcinomas.

RADTAC: A subcellularly targeted anti-CD70 radiotheranostic to overcome therapeutic resistance in kidney cancer

Team Leaders: Steve Cho, M.D., and Phuoc Tran, M.D., Ph.D.

This project will develop a new treatment for patients with renal cell carcinoma, the most common adult kidney cancer, that have already failed with other treatments, using RADiopharmaceutical TArgeted Chimera (RADTAC). UT MD Anderson invented RADTAC, a drug discovery and radiotheranostic platform designed to precisely deliver radiotherapy inside the cancer cell’s nucleus. This is expected to concentrate cell damage while minimizing off-target toxicity.

Replacing uncertainty with learning: PREcision DIagnostics and Clinical Trajectory prediction for Colorectal Liver Metastases (PREDICT-CLM)

Team Leaders: Kristy Brock, Ph.D., and Bruno Odisio, M.D., Ph.D.​

Colon cancer with liver metastases is considered stage 4 disease and generally only about 15% of patients live past five years. This project will create a large, secure database that combines patient information, medical test results and treatment decisions made by physicians. Using this information, researchers will develop a digital twin called PREDICT-CLM that can simulate different treatment options and predict possible outcomes for each patient.

Triple-I intercept: Precision interception of lung cancer evolution driven by injury, inflammation and IL-1 signaling

Team Leaders: Humam Kadara, Ph.D., Seyed Moghaddam, M.D., and Jianjun Zhang, M.D., Ph.D.

Chronic injury to the lungs — such as smoking, air pollution and respiratory viral injury — may elevate the risk of lung adenocarcinoma, the most common type of non-small cell lung cancer, but currently we have limited understanding of the role injury and inflammation play in the development of this cancer type. This project aims to better understand that link, develop biomarkers to guide the management of early lesions and establish clinical strategies for interrupting the development of this cancer.

Decoding “luck” in cervical cancer radiation therapy: A spatially explicit digital twin program to personalize care and improve patient-specific outcomes

Breakthrough Discoveries Program Impact Seed Award recipient

Team Leaders: Lilie Lin, M.D.,​ and Heiko Enderling, Ph.D.

Cervical cancer remains a major health burden with highly variable treatment response. This project will develop a platform for delivering highly targeted radiation treatment using a digital twin framework to generate patient-specific recurrence risk predictions and risk-adaptive treatment strategies.