Cancer therapy that stops tumour growth without damaging healthy cells

The future of cancer treatments could be changed by a major breakthrough made by the Francis Crick Institute in collaboration with Vividion Therapeutics.

Researchers have identified a compound that stops tumour growth by inhibiting the signals that cause cancer cells to divide – and the best thing is that the treatment does not harm good tissue, as regular chemotherapy does.

Published in Science this month, the study shows that the new compound prevents the RAS gene – mutated in around one in five cancers – from connecting with a key enzyme called PI3K, which helps control how cells grow. RAS becomes permanently active when it mutates. This leads to uncontrolled cell division, and the formation of tumours.

Targeting cancer’s “on-switch” safely

RAS was a hard target to hit because shutting off the RAS completely disrupts normal cell function, causing severe side effects like hyperglycaemia. The Crick team, however, found a way to selectively block the connection between RAS and PI3K while leaving PI3K’s other essential functions — like insulin regulation — untouched.

In tests on mice with lung tumours mutated by RAS, the treatment stopped tumour development without raising blood sugar levels. The therapy was even more effective and lasting when combined with other cancer drugs.

Julian Downward Principal Group Lead of the Oncogene Biology Laboratory, Crick Institute, said that “our collaborative effort has overcome the challenge by targeting the PI3K/RAS interaction, leaving PI3K unrestricted to bind its other targets.” It’s exciting that these clinical trials have begun, as it shows the power of understanding fundamental biology and chemistry to find something that can help people with cancer.

The treatment proved to be effective also against HER2-mutated cancerous breast tumours. This suggests that the treatment could treat a broader spectrum of cancers other than those caused by RAS.

Human trials are now underway

The phase one clinical trial of the new compound is now complete. It will test for safety and side-effects in patients with mutations RAS and/or HER2. The trials will also examine how the compound works when combined with RAS-targeting treatments.

Matt Patricelli (Ph.D.), Chief Scientific Office of Vividion said, “By creating molecules that block RAS from connecting to PI3K, while allowing healthy cell functions to continue, our team has found a way selectively to block a cancer growth signal. It’s very rewarding to see the science moving forward in the clinic. This has the potential to have a significant impact on the lives of patients.

Breast Cancer Awareness Month

This discovery comes during Breast Cancer Awareness month, an important time for research in the fight against this disease. The number of breast carcinoma cases is on the rise. However, breakthroughs such as this one offer renewed hope for patients and families.

Global collaborations such as this one, which move from the lab to the clinic, represent a step forward for all of us in making cancer treatments safer and more targeted a reality.

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