An international team of researchers from the UK and China has made significant strides in understanding and potentially overcoming one of the greatest challenges in cancer treatment: chemotherapy resistance.

Led by The Institute of Cancer Research (ICR) in London and Sun Yat-sen University in China, this early-stage research utilized mice to explore new avenues for combating cancer. The team discovered that Stiripentol, a drug currently used for epilepsy, can reverse cancerâ™s resistance to chemotherapy, leading to tumor shrinkage and prolonged survival rates (1^✔

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Stiripentol (Diacomit): For Severe Myoclonic Epilepsy in Infancy

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The study zeroed in on lactate, a byproduct that accumulates as cancer cells convert nutrients to energy. This substance was found in high concentrations within chemotherapy-resistant cancer tissues. By targeting lactate, the researchers hoped to disrupt its role in chemotherapy resistance.

Published in the journal Nature, the research examined tissue samples from 24 stomach cancer patients. Among these, 15 had chemotherapy-resistant cancers with tumors that continued to grow despite treatment. This analysis provided crucial insights into the role of lactate in fostering resistance.

In experiments with mice, the combination of Stiripentol and chemotherapy resulted in tumor size reduction for four weeks post-treatment and extended survival for over 70 days. In contrast, mice treated only with chemotherapy saw tumor reduction for merely one week, with none surviving beyond 40 days.

Impact on DNA Repair Proteins

Further investigation revealed that lactate alters the structure and efficiency of NBS1, a key protein involved in DNA repair. This alteration is believed to contribute to chemotherapy resistance.

The researchers suggest that lactate might also be responsible for chemotherapy resistance in other types of cancer, such as pancreatic, lung, and ovarian cancers. This discovery could pave the way for more effective treatments across various cancer types.

"This highly promising research has identified a potential mechanism for how cancer evades chemotherapy," said Professor Axel Behrens, Professor of Stem Cell Biology at The Institute of Cancer Research. "Our early-stage study indicates that preventing lactate buildup can make previously resistant tumors sensitive to chemotherapy again, allowing the treatment to remain effective," Axel added.

This groundbreaking research offers hope for new strategies to overcome chemotherapy resistance, potentially improving outcomes for countless cancer patients worldwide.

Reference:

1. Stiripentol (Diacomit): For Severe Myoclonic Epilepsy in Infancy - (https://www.ncbi.nlm.nih.gov/books/NBK349345/)

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