Targeting the PI3K/AKT pathway for the treatment of prostate cancer.
Despite recent advances in our understanding of the biological basis of prostate cancer, the management of the disease, especially in the castration-resistant phase, remains a significant challenge. Deregulation of the phosphatidylinositol 3-kinase pathway is increasingly implicated in prostate carcinogenesis. In this review, we detail the role of this pathway in the pathogenesis of prostate cancer and the rapidly evolving therapeutic implications of targeting it. In particular, we highlight the importance of the appropriate selection of agents and combinations, and the critical role of predictive and pharmocodynamic biomarkers.
Sarker
Debashis
D
Section of Medicine and Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, United Kingdom.
Reid
Alison H M
AH
Yap
Timothy A
TA
de Bono
Johann S
JS
D059002:Androgen Receptor Antagonists; D018925:Chemokines / Q000378:metabolism; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
D059002:Androgen Receptor Antagonists; D018925:Chemokines; D015514:Oncogene Proteins, Fusion; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011944:Receptors, Androgen; D012697:Serine Endopeptidases; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C072312:ERG protein, human; C515553:TMPRSS2-ERG fusion protein, human; C494929:PTEN protein, human; C421305:TMPRSS2 protein, human