Rheb's role in cancer

Aug 14, 2008

Two independent papers in the August 15th issue of G&D identify the Rheb GTPase as a novel oncogene and a promising new chemotherapeutic target.

The first paper, from Dr. Pier Paolo Pandolfi (BIDMC and Harvard Medical School) and colleagues, demonstrates that the Ras-like small GTPase, Rheb, is directly involved in prostate tumorigenesis.

Through the overexpression of Rheb specifically in prostate tissue of live mice, the researchers were able to show that increased Rheb signaling activity is sufficient to induce low-grade prostate neoplasias. Furthermore, in combination with decreased PTEN activity, Rheb overexpression can stimulate aggressive prostate tumor 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," explains Dr. Pandolfi.

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

Using an experimental animal model of human lymphoma, the researchers demonstrated that Rheb overexpression contributes to lymphoma formation. They also pinpointed Rheb overexpression as a naturally occurring genetic mutation in human patient-derived lymphoma tumor samples. In addition, Dr. Wendel and colleagues found that the targeted inhibition of Rheb can effectively counteract tumor progression in lymphomas with this unique genetic signature.

Dr. Wendel emphasizes that "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."

Source: Cold Spring Harbor Laboratory

Explore further: Cancer diagnosis and treatment need improvement

add to favorites email to friend print save as pdf

Related Stories

As dust clears, what's next for Sony?

3 hours ago

The Sony hacking attack continues to deliver more dramatic plotlines than any fictional movie, but meanwhile the movie studio must move forward and tackle the next steps in minimizing the mess. Will Sony ...

Recommended for you

Suppressing a protein reduces cancer spread in mice

7 hours ago

Scientists have found that decreasing the levels of or blocking a specific protein commonly found in humans and many other animals allowed them to slow the spread of two different kinds of cancer to the lungs ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.