Research reveals how cancer resists chemotherapy and identifies a way to counteract it.

New Delhi: An international team of researchers from the UK and China has made a significant breakthrough in understanding how cancer develops resistance to chemotherapy, one of the major obstacles in treating this deadly disease.

The study, led by The Institute of Cancer Research (ICR) in London and Sun Yat-sen University in China, focused on the use of Stiripentol—a drug traditionally used to treat epilepsy—to reverse chemotherapy resistance in cancer. Early-stage research involving mice demonstrated that Stiripentol can shrink tumors and prolong survival when combined with chemotherapy.

The researchers identified lactate, a byproduct of cancer cells metabolizing nutrients for energy, as a key factor in chemotherapy resistance. Lactate was found in higher concentrations in chemotherapy-resistant cancer tissues.

Published in the journal Nature, the study involved examining tissue samples from 24 patients with stomach cancer, out of which 15 had tumors that were resistant to chemotherapy and continued to grow despite treatment.

In the experimental phase with mice, those treated with a combination of Stiripentol and chemotherapy showed significant tumor reduction for four weeks post-treatment and survived over 70 days. In contrast, mice treated with only chemotherapy experienced tumor shrinkage for just one week before the tumors resumed growth, with none surviving beyond 40 days after treatment.

The researchers discovered that lactate affects the structure and efficiency of NBS1, a crucial protein involved in DNA repair, further contributing to chemotherapy resistance.

The findings suggest that lactate may play a similar role in resistance in other cancers, such as pancreatic, lung, and ovarian cancers. The study’s lead author, Professor Axel Behrens, Professor of Stem Cell Biology at ICR, highlighted the significance of this discovery. "This extremely promising research has uncovered a likely mechanism for how cancer evades chemotherapy," Behrens stated. "In our early-stage study, we've seen that you can prevent the build-up of lactate and make a tumor that was resistant to chemotherapy sensitive again—the treatment continues to work."

This research offers hope for improving the effectiveness of chemotherapy by targeting lactate build-up, potentially enhancing treatment outcomes for patients with various chemotherapy-resistant cancers.