Inhibiting PI3K as a therapeutic strategy against cancer.
Class I PI3K is composed of heterodimeric lipid kinases regulating essential cellular functions including proliferation, apoptosis and metabolism. Class I PI3K isoforms are commonly amplified in different cancer types and the PI3Kalpha catalytic subunit, PIK3CA, has been found mutated in a variable proportion of tumours of different origin. Furthermore, PI3K has been shown to mediate oncogenic signalling induced by several oncogenes such as HER2 or Ras. These facts suggest that PI3K might be a good target for anticancer drug discovery. Today, the rise of PI3K inhibitors and their first in vivo results have cleared much of the path for the development of PI3K inhibitors for anticancer therapy. Here we will review the PI3K pathway and the pharmacological results of PI3K inhibition.
Paz-Ares
Luis
L
Medical Oncology, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Blanco-Aparicio
Carmen
C
García-Carbonero
Rocío
R
Carnero
Amancio
A
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors