Targeting the PI3K–Akt pathway in kidney cancer

Abstract

Kidney cancer, or renal cell carcinoma, is a relatively rare malignancy but is metastatic at diagnosis in a third of patients; metastatic disease has a dismal prognosis. Conventional chemotherapy has been woefully inadequate, thus novel targets for ‘designer’ therapies are being actively evaluated. The PI3K–Akt signaling cascade, owing to its dual role in both survival and mitogenic signaling, is in theory an ideal therapeutic target for this disease, but may also represent its fatal flaw. Thus, largely due to toxicity issues, no PI3K or Akt inhibitors are currently ready for clinical application. In this review, we discuss PI3K–Akt inhibitors as well as inhibitors of pathways and targets both immediately up- and downstream of this cascade, many of which show promise in the clinic.

Keywords::

• Akt
• inhibitors
• PI3K
• receptor tyrosine kinase
• renal cell carcinoma

Acknowledgements

This work was supported by grant 1R21CA 91259–01A1 and the Early Detection Research Network, both from the US National Cancer Institute, the University of California Cancer Research Coordinating Committee and the Morris Animal Foundation.