Study shows how cancer evades chemotherapy, finds mechanism to reverse

New Delhi: An international team of researchers from the UK and China has shown how cancer builds up resistance to chemotherapy — one of the biggest challenges in the treatment of the deadly disease. Using a mice study, the early-stage research, led by The Institute of Cancer Research (ICR), London, and Sun Yat-sen University, China showed that Stiripentol — a drug currently used to treat epilepsy — can help reverse cancer’s resistance to chemotherapy, which will help shrink tumours and prolong survival. In the study, the team zeroed in on lactate — the product that builds up as cancer cells convert nutrients to energy — which was found to be most abundant in chemotherapy-resistant cancer tissues. For the study, published in the journal Nature, the researchers examined tissue from 24 patients with stomach cancer, where 15 of the cancers were resistant to chemotherapy and the tumours had continued to grow. Stiripentol and chemotherapy reduced the size of tumours — for four weeks after treatment — in mice with stomach cancer. These also survived for longer — for more than 70 days. In comparison, tumours in mice treated with chemotherapy alone shrunk for one week and started to grow again. With only chemotherapy, no mice survived for longer than 40 days after treatment. Further, lactate was also found responsible for altering the structure of a key protein involved in DNA repair, called NBS1, and affecting its efficiency. The researchers believe that lactate may be behind chemotherapy resistance in other cancers such as “pancreatic, lung and ovarian cancers”. “This extremely promising research has uncovered a likely mechanism for how cancer evades chemotherapy,” said Professor Axel Behrens, Professor of Stem Cell Biology at The Institute of Cancer Research. “In our early-stage study, we’ve seen that you can prevent the build-up of lactate and make a tumour that was resistant to chemotherapy sensitive again — the treatment continues to work,” Axel added.

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