Reference News Network, October 21 report: According to the website of the US "Science Daily" on October 19, scientists from the Francis Crick Institute in the UK and Vividion Therapeutics discovered a compound that can precisely prevent the oncogenic gene RAS from binding to key pathways of tumor growth.

This potential therapy has entered its first human clinical trial. If proven safe and effective, it could become a new approach to treat multiple cancers while minimizing damage to healthy cells.

The RAS gene plays a central role in regulating cell growth and division, but mutations in this gene occur in about one-fifth of cancer cases. Once mutated, RAS remains constantly active and continuously sends signals, prompting cells to grow and proliferate continuously.

Inside the cell, RAS is attached to the cell membrane and serves as the starting signal for a series of growth processes. It has been proven difficult to completely inhibit RAS or the enzymes it controls, as these pathways are crucial for normal cell function. One enzyme related to RAS, called PI3K, also regulates blood sugar through insulin. Completely blocking PI3K could lead to side effects such as high blood sugar.

The team's research findings were published in the journal "Science" on October 9. By combining chemical screening with biological testing, they discovered compounds that can prevent RAS from interacting with PI3K without affecting normal cellular activities.

Vividion Therapeutics researchers identified a group of small molecules that can permanently attach to specific sites on the surface of PI3K, where RAS usually binds. Using detection methods developed by the Francis Crick Institute, they confirmed that these compounds successfully blocked the interaction between RAS and PI3K, while not interfering with PI3K's other functions, including those related to insulin signaling.

Subsequently, the Francis Crick Institute team and their collaborators at Vividion Therapeutics tested one of these compounds in mice with RAS-mutated lung tumors. The therapy successfully inhibited tumor growth, and the researchers found no signs of elevated blood sugar levels.

Next, they tried combining this new compound with two other drugs targeting the same pathway enzymes. The results showed that the combination therapy had a stronger and more prolonged effect on inhibiting tumor growth than any single drug.

Scientists also tested the compound in mice with another type of mutated oncogene, HER2. The HER2 gene is often overactive in breast cancer and is also associated with PI3K. The results showed that tumor growth was again blocked, although this effect did not depend on RAS. This finding suggests that the new compound may be used to stop the growth of more types of cancer.

Currently, the drug has entered its first human clinical trial targeting patients with dual mutations in RAS and HER2, aiming to test its safety and side effects. The trial will also evaluate whether this potential therapy, when combined with other RAS-targeting drugs, can produce better efficacy.

Julian Downward, Head of the Oncogene Biology Laboratory at the Francis Crick Institute, said: "Given that the RAS gene is mutated in many cancers, we have been exploring for years how to prevent it from interacting with cell growth pathways, but side effects have always hindered the development of therapies."

Downward said: "By specifically targeting the interaction between PI3K and RAS, while allowing PI3K to freely bind to other targets, our collaborative research has finally solved this problem. It is exciting to see the start of clinical trials. This fully demonstrates that understanding the principles of chemistry and basic biology can lead to ways that might help cancer patients."

Matteo Patricelli, Chief Scientific Officer of Vividion Therapeutics, said: "This discovery could open up new avenues for cancer treatment. By designing molecules that can block the interaction between RAS and PI3K while not affecting the normal activity of healthy cells, we have found a way to selectively block key cancer growth signals. Seeing this research move toward the clinic, which has the potential to bring real changes to patients, fills us with immense satisfaction." (Translated by Liu Zongya)

Original article: https://www.toutiao.com/article/7563646296972706338/

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