Targeting the PI3K-Akt pathway in kidney cancer.
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.
Park
Jin-Young
JY
Division of Nephrology, Department of Internal Medicine, Immunology Graduate Group, University of California, Davis, CA 95616, USA. jyppark@ucdavis.edu
Lin
Pei-yin
PY
Weiss
Robert H
RH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt