Scientists Discover Breakthrough Method to Target Treatment-Resistant Cancers - Video

Cancer's greatest trick is evolving to beat our drugs-but what if we turned that evolution against it? An international team led by Israel's Weizmann Institute of Science has developed a groundbreaking strategy that harnesses drug-resistance mutations themselves to create new immunotherapies. Published in Cancer Discovery, their computational tool SpotNeoMet identifies shared “neo-antigens”—unique protein fragments on resistant cancer cells-that could train the immune system to attack tumors broadly across patients.

One of the toughest battles in oncology is therapy resistance, where cancers mutate to dodge treatments like hormone blockers or chemotherapy, especially in metastatic stages. Instead of fighting these mutations, the researchers propose flipping the script: using them as targets for immunotherapy. SpotNeoMet scans genomic data from thousands of patients to pinpoint resistance mutations that produce neo-antigens exclusive to cancer cells, making them ideal for immune recognition without harming healthy tissue.

The team applied their method to metastatic prostate cancer, where nearly all patients eventually develop resistance to standard therapies. Analyzing tumor sequencing data, SpotNeoMet flagged three promising neo-antigens from common resistance mutations. In lab tests and mouse models, these neo-antigens successfully triggered strong T-cell responses, selectively killing cancer cells while sparing normal ones.

Unlike hyper-personalized vaccines tailored to single patients, this approach targets mutations shared by large patient groups, enabling “off-the-shelf” treatments. “The mutations letting tumors evade drugs become their Achilles’ heel through precise immunotherapy,” said lead researcher Prof. Yardena Samuels. Early results suggest broad applicability beyond prostate cancer to other resistant malignancies like breast or lung cancers.

The discovery shifts the paradigm from outsmarting cancer’s adaptations to exploiting them. By crowdsourcing resistance neo-antigens across global datasets, SpotNeoMet paves the way for scalable, mutation-agnostic immunotherapies that could revive hope for patients whose options have run dry.

REFERENCE: Nofar Gumpert. Et al.; Recurrent Immunogenic Neoantigens and Their Cognate T-cell Receptors in Treatment-Resistant Metastatic Prostate Cancer. Cancer Discov 2025; https://doi.org/10.1158/2159-8290.CD-24-1213