Unlocking chemo-resistance in cancer

Credit: CC0 Public Domain

La Trobe University researcher Associate Professor Hamsa Puthalakath is the first scientist to have unlocked a long-standing mystery as to why some cancers do not respond to treatment with one of the most effective chemotherapy drugs: 5-Fluorouracil (5-FU).

"We are now working to develop a drug that will make 5-FU effective in cancers previously resistant to treatment," Associate Professor Puthalakath said.

The research also has potential to lead to a lab test to check for 5-FU resistance, reducing unnecessary treatments.

5-FU (Trade name Adrucil/Carac/Efudex) is on the World Health Organization's Model List of Essential Medicines. It is used to fight colorectal, breast, head, neck and aero-digestive cancers, but acquired resistance in response to treatment is a major problem and up to half of colorectal cancer patients with metastasis become resistant to 5-FU.

In a paper published today in the Proceedings of the National Academy of Sciences (PNAS), Associate Professor Puthalakath explains, for the first time, the precise mechanism by which cancer develops resistance to 5-FU.

He links 5-FU resistance to a little-understood protein called "BOK". Associate Professor Puthalakath said scientists have puzzled over BOK's function for decades, with many arguing its function to be redundant.

"I have always believed that nature keeps proteins for a reason," Associate Professor Puthalakath said. "Our research shows BOK binds with an enzyme called UMPS, enhancing cells' ability to proliferate. Without BOK, cells struggle to synthesize DNA, and they can't proliferate. The same enzyme is also responsible for converting 5-FU into its toxic form in cancer. Therefore, to avoid 5-FU's toxicity, turn off BOK."

Cancer cells then become dormant and take up less toxic 5-FU, enabling them to survive chemotherapy treatment before mutating to become even more aggressive.

Associate Professor Puthalakath's research, funded by La Trobe University (RFA) and the Swiss National Science Foundation, tested samples from cancer patients. He found those patients who had responded to 5-FU treatment had BOK, while those who hadn't responded to the chemotherapy had no BOK.

"This shows that without BOK present, there is no point attempting to use 5-FU as an effective chemotherapy treatment," Associate Puthalakath said.

"In understanding the science behind chemotherapy resistance, we think that we have found 's 'Achilles heel' and this has significant implications for future drug development."

Explore further

Long exposure to protein inhibitor may be key to more effective chemotherapy for cancer

More information: Rahul Srivastava el al., "BCL-2 family protein BOK is a positive regulator of uridine metabolism in mammals," PNAS (2019). www.pnas.org/cgi/doi/10.1073/pnas.1904523116
Citation: Unlocking chemo-resistance in cancer (2019, July 15) retrieved 22 August 2019 from https://medicalxpress.com/news/2019-07-chemo-resistance-cancer.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

Feedback to editors

User comments

Jul 15, 2019

I have been suffering from HIV and Genital Herpes for the past 3 years and 8 months, and ever since then i have been taking series of treatment but there was no improvement until i came across testimonies of Dr TAKUTA on how he has been curing different people from different diseases all over the world, then i contacted him as well. After our conversation he sent me the medicine which i took according to his instructions. When i was done taking the herbal medicine i went for a medical checkup and to my greatest surprise i was cured from Herpes. My heart is so filled with joy. If you are suffering from Herpes or any other disease you can contact Dr TAKUTA today on this Email address: takutaspellalter@gmail.com or WhatsApp him on this Tell.Number +27788634102....

Dr.TAKUTA also cures:
2. HERPES 1/2
5.STDS and STI

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more