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Two independent papers in the August 15th number of G&D identify the Rheb GTPase as a novel transforming gene and a promising newfangled 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 gland tissue of live mice, the researchers were able-bodied to establish that increased Rheb signal activity is sufficient to induce low-grade prostate neoplasias. Furthermore, in combination with decreased PTEN activity, Rheb overexpression keister stimulate belligerent 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 ar already testing such drugs alone, and in combination with other chemotherapeutics in faithful animate being models," explains Dr. Pandolfi.
In the attendant paper, Dr. Hans-Guido Wendel (Memorial Sloan Kettering Cancer Center) and colleagues stage evidence that Rheb can also function as an oncogene in lymphomagenesis.
Using an experimental beast model of human lymphoma, the researchers demonstrated that Rheb overexpression contributes to lymphoma formation. They as well pinpointed Rheb overexpression as a course occurring hereditary mutation in human patient-derived lymphoma tumor samples. In addition, Dr. Wendel and colleagues establish that the targeted inhibition of Rheb can efficaciously 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 designate patients that will benefit from relatively non-toxic therapies with targeted drugs like rapamyicn or inhibitors of the farnesyltransferase enzyme."
Source:
Heather Cosel-Pieper
Cold Spring Harbor Laboratory
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