'Undruggable' cancer molecule blocked by new approach

In collaboration with the Press Association

An important cancer molecule previously thought 'undruggable' could be blocked by a new targeted approach, according to US researchers.

The work could be a crucial early step towards a drug that acts against several different types of cancer.

"This is the start of a long road of development that could result in a new type of drug treatment in the future" - Professor Julian Downward, Cancer Research UK

The scientists focused on a molecule called Ras, which is faulty in around three out of 10 cancers. They developed compounds that stick to a small pocket in one of several cancer-causing forms of the molecule, without binding to the normal form.

This offers a newly discovered 'Achilles heel' as the compounds attach irreversibly and could stop other cancer-linked molecules from receiving signals from Ras.

When tested on human lung cancer cells grown in the lab, the compounds efficiently killed the cells that rely on this form of Ras for survival, according to the study published in the journal Nature.

The discovery paves the way for future drug development that could benefit patients with several common cancers, according to the scientists at the Howard Hughes Medical Institute and the University of California San Francisco (UCSF) Department of Cellular and Molecular Pharmacology.

Ras is the most commonly activated molecule in lung tumours and bowel cancers.

Changes in Ras are also seen in the majority of pancreatic cancers, which is notoriously difficult to treat.

Professor Julian Downward, a expert on Ras from the Cancer Research UK London Research Institute, said: "This study is a big step forward in finding ways to shutdown important cancer-driving molecules like Ras that have been extremely difficult to develop drugs against."

"Designing molecules that seek out and selectively block a hyperactive form of Ras that can lead to cancer is a very exciting approach. This is the start of a long road of development that could result in a new type of drug treatment in the future."

"Changes to Ras are extremely common in cancer and work over the last 25 years from labs around the world, including my own, has focussed on understanding how these changes contribute to cancer to find new ways to treat the disease."

Copyright Press Association 2013

References

  • Ostrem J.M, et al. (2013). K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions, Nature, DOI: