The mTOR (mammalian target of rapamycin) pathway represents a convergence point for signalling pathways commonly disrupted in cancer. The pathway includes several known and putative oncogenes as well as tumour suppressors. Rheb GTPase is the upstream activator of the mTOR Complex 1 (mTORC1) and is itself activated by growth factors and nutrients.
Two independent papers in the August 15th issue of Genes and Development link Rheb activity with particular cancers. Wendel et. al. demonstrate that Rheb activation can produce rapid development of aggressive and drug-resistant lymphomas. The authors further show that activation of mTORC1 is dependent on farnesylation of Rheb and that an inhibitor of farnesyl transferase (FTI) is able to block the activation. It is noted that Rheb is highly expressed in certain human lymphomas.
Pandolfi et. al. show that overexpression of Rheb promotes hyperplasia and a low-grade neoplastic phenotype in the mouse prostate. Additionally, Rheb overexpression combined with Pten haploinsufficiency results in marked promotion of prostate tumorigenesis.
These results suggest potential for Rheb as a therapeutic target in particular oncology indications.