Phosphatidylinositol 3 kinase (PI3K) inhibitors as new weapon to combat cancer

Phosphatidylinositol-3 kinase (P13K) pathway is one of the most frequently activated pathogenic signaling cascades in human malignancies. P13K is genetically mutated or overexpressed in a wide variety of cancers including ovarian, breast, prostate, gastric, colorectal, glioblastoma, endometrial and brain cancers. Studies are still ongoing to find more efficient and selective P13K inhibitors or dual P13K inhibitors to overcome the resistance to the current inhibitors. This review will focus on the three main classes of P13K inhibitors with efficacious antitumor activity which are: isoform-selective P13K inhibitors, dual pan-Class 1 PI3K/m-TOR inhibitors, and pan-Class I PI3K inhibitors without significant m-TOR activity. Isoform-selective P13K inhibitors are classified into four classes IA, IB, II, and III. Moreover, SAR among each class, together with the biological activity will be discussed. In addition, the new scopes for the design of novel candidates to overcome emerging resistance will be highlighted as well. (C) 2019 Elsevier Masson SAS. All rights reserved.