They discover why some cancers do not respond to fluoruracil treatment

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The researcher of the La Trobe University, in Australia, and associate professor Hamsa Puthalakath is the first scientist to discover why some cancers do not respond to treatment with one of the most effective chemotherapy drugs, 5-fluorouracil (5-FU), as published in the journal Proceedings of the National Academy of Sciences (PNAS).

“We are now working to develop a drug that will make 5-FU effective in cancers that were previously resistant to treatment,” he explains.

5-FU is on the list of essential medicines of the World Health Organization, but resistance acquired in response to treatment is a major problem and up to half of colorectal cancer patients with metastases become resistant to 5-FU .

The authors explain in this research, for the first time, the precise mechanism by which cancer develops resistance to 5-FU. Link the resistance to this drug to a little known protein called BOK. So far scientists have been intrigued by BOK's function for decades, and many argue that its function is redundant.

“I have always believed that nature preserves proteins for a reason explains Puthalakath. Our research shows that BOK binds with an enzyme called UMPS, which improves the ability of cells to proliferate. Without BOK, cells fight to synthesize DNA, and cannot proliferate. The same enzyme is also responsible for converting 5-FU into its toxic form for cancer. Therefore, to avoid the toxicity of 5-FU, cancer cells deactivate BOK. ”

Thus, cancer cells become inactive and take less toxic 5-FU, which allows them to survive chemotherapy treatment before mutating to become even more aggressive.

The authors analyzed samples of cancer patients and found that those who had responded to 5-FU treatment had BOK, while those who had not responded to chemotherapy did not have BOK.
“This shows that without the presence of BOK, it makes no sense to try to use 5-FU as an effective chemotherapy treatment,” says Puthalakath. By understanding the science behind chemotherapy resistance, we believe we have found the Achilles heel of cancer and this has important implications for the future development of medications. ”


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