Scientists Identify Gene That Holds Key to New Chemotherapeutic Target

by Rajashri on Aug 16 2008 6:00 PM

Two independent studies have found that a gene, called the Rheb GTPase, which is a novel oncogene, holds promise as a new chemotherapeutic target.

In the first study, authored by Dr. Pier Paolo Pandolfi (BIDMC and Harvard Medical School) and colleagues, the scientists showed that the Ras-like small GTPase, Rheb, is directly involved in prostate tumorigenesis.

Rheb's overexpression, specifically in prostate tissue of live mice enabled the researchers to show that increased Rheb signalling activity was enough to induce low-grade prostate neoplasias.

Also, when combined with decreased PTEN activity, Rheb overexpression can stimulate aggressive prostate tumour formation.

"The identification of Rheb as a gene involved in the pathogenesis of cancer opens new avenues for the development of anti-cancer therapies, as Rheb is an inherently 'druggable' target. Indeed, we are already testing such drugs alone, and in combination with other chemotherapeutics in faithful animal models," explained Dr. Pandolfi.

In the accompanying paper, Dr. Hans-Guido Wendel (Memorial Sloan Kettering Cancer Center) and colleagues gave evidence that Rheb can also function as an oncogene in lymphomagenesis.

The researchers used experimental animal model of human lymphoma, and demonstrated that Rheb overexpression triggers lymphoma formation. They also pinpointed Rheb overexpression as a naturally occurring genetic mutation in human patient-derived lymphoma tumor samples.

Besides, they also found that the targeted inhibition of Rheb can effectively counteract tumor progression in lymphomas with this unique genetic signature.

"The key clinical implication is that Rheb levels in tumor tissue could indicate patients that will benefit from relatively non-toxic therapies with targeted drugs like rapamyicn or inhibitors of the farnesyltransferase enzyme," said Wendel.

The two studies are published in the latest issue of G and D.