New research reveals the mechanisms by which cancer cells develop resistance

new study by the Australian team found that once exposed to targeted cancer drugs, cancer-related genes significantly increase the chances of mutation during replication, allowing cancer cells to develop resistance. The study, published in the new issue of the American journal Science, promises to open up new cancer strategies.To reveal potential factors affecting cancer resistance, teams from the Australian Gavin Institute of Medicine and others analyzed biopsy samples of cancer patients before and after targeted treatment. The study found that cancer cells in patients who had been targeted showed higher levels of DNA (deoxybonucleic acid) damage than pre-treatment samples.Cancer cells exposed to targeted therapy are significantly more likely to develop random genetic mutations than cancer cells that are not exposed to anti-cancer drugs, a mechanism known as stress-induced mutations that can be used by melanoma, pancreatic cancer, breast cancer and other cancers to develop resistance, the researchers explained.Studies have revealed that the repamycin target protein (MTOR) plays a key role in "stress-induced mutations" in cancer cells. The protein is like a pressure sensor that tells normal cells to stop growing when they encounter environmental pressure, and when cancer cells encounter anticancer therapy, it alters gene expression associated with DNA replication and repair of cancer cells, such as making polymerases responsible for DNA replication "error-prone" from a "high fidelity" state. This leads to more genetic mutations in cancer cells and ultimately contributes to their resistance.David Thomas, a professor at the Gavin Institute of Medicine who led the study, told Xinhua that such genetic mutations can alter the shape of certain proteins, making targeted cancer drugs that target them ineffective.The study further found that increasing the rate of errors in gene replication was only temporary, and that cancer cells developed resistance and returned to the normal process of high-quality DNA replication to ensure their survival. "Although the increased rate of gene mutation increases the likelihood that cancer cells will develop resistance, it also randomly destroys other parts of the cell, which can have harmful effects on the cancer cells themselves." Thomas explained.Based on the study, the team proposed combining conventionally targeted anti-cancer drugs with drugs that target DNA repair mechanisms to improve existing anti-cancer therapies. Animal experiments have shown that combined drug use significantly reduces cancer cell growth in mice compared to using only targeted anti-cancer drugs. (Xinhua
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