The effective treatment of cancer requires the ability to destroy cancerous cells. Nearly one third of all cancers today involve mutations of the Kras gene, which has proven resistant to existing cancer treatments.

The current prognosis for patients with mutant-Kras cancers is poor because there is no effective treatment. However, recent analysis by Livio Mallucci of King’s College London and Valerie Wells of NYU London may present a new method to combat these untreatable cancers.

In a feature article in Drug Discovery Today, Mallucci and Wells discuss the current therapeutic strategies and their limitations and highlight a new way forward using the recombinant form of a physiological protein molecule, beta-GBP, which has proven to be effective against human Kras-driven tumors in animal models.

There are several significant
aspects to their discovery. First, the beta-GBP molecule they have identified kills mutant Kras, and other cancer cells, by activating alternative routes to destroy cancer while leaving normal cells unharmed. Second, the beta-GBP molecule is naturally occurring in the body as a physiological molecule and therefore would avoid the complexity of current combinatorial therapies and the issues of drug resistance, toxicity, and all side effects experienced with chemotherapy. Finally, translation of beta-GBP to the clinic, facilitated by its physiological nature, could open a new therapeutic opportunity representing a significant step forward in the treatment of cancers resistant to all current treatments.

Mallucci and Wells stress that rather than relying on current strategies, there are times when therapeutics requires nonconventional thinking and daring. They have shown that mutant Kras, widely regarded as “undruggable,” yields to a treatment which, by impairing physiological processes rather than impairing targets, forces tumor cells to die while leaving normal cells  

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