Tumor cells, notorious for their adaptability and resilience during treatment, have met their match in a groundbreaking study led by experts at Massachusetts General Hospital (MGH). Published in Cancer Discovery, the study introduces BipotentR, a cutting-edge computational tool designed to simultaneously cripple tumor energy sources and reinvigorate the immune system’s fight against cancer.

Dr. Keith T. Flaherty, Director of Clinical Research at the MGH Cancer Center, and his team harnessed the power of BipotentR to identify key proteins governing both cancer cell metabolism and immune response within tumors. This innovative tool not only pinpointed these crucial targets but also provided insights into patient outcomes following immunotherapy.

BipotentR, fueled by artificial intelligence, analyzed gene expression data from immunotherapy-treated cancer patients, cell lines, and animal models. It uncovered 38 cancer cell-specific immune-metabolic regulators, with Estrogen Related Receptor Alpha (ESRRA) emerging as a top candidate. Remarkably, ESRRA was found to be highly active in immunotherapy-resistant tumors across various cancer types.

Inhibiting ESRRA proved to be a potent strategy, effectively dismantling tumors by undermining their energy metabolism while activating distinct immune mechanisms. Crucially, experiments in mice demonstrated the safety and specificity of ESRRA inhibition, sparing healthy tissue from harm.

The potential of BipotentR extends beyond ESRRA, offering a valuable resource for identifying drugs that target specific cancer-related pathways while stimulating the immune system’s response. This breakthrough not only opens novel therapeutic avenues but also serves as a biomarker for predicting patient responses to immunotherapy.

The collaborative effort, with co-authors including Phillip Munson, Dejan Juric, and David E. Fisher from MGH, received crucial support from the Adelson Medical Research Foundation. This underscores the significance of partnerships and funding in advancing scientific discovery.

With BipotentR, researchers now possess a powerful tool to identify and target specific cancer pathways while leveraging the body’s natural defenses. This approach not only promises more effective treatments but also marks a new era of personalized cancer care, heralding a brighter future for cancer therapy.

By Impact Lab