The phosphatidylinositol-3 kinase (PI3K) pathway is one of the\nmost frequently activated pathogenic signalling routes in\nhuman cancers, making it a rational and important target for\ninnovative anticancer drug development and precision\nmedicine. The three main classes of PI3K inhibitors currently in\nclinical testing comprise dual pan-Class I PI3K/mTOR inhibitors,\npan-Class I PI3K inhibitors lacking significant mTOR activity and\nisoform-selective PI3K inhibitors. A major step forward in recent\nyears is the progression of over 30 small molecule PI3K inhibitors\ninto clinical trials and the first regulatory approval of the PI3Kd\ninhibitor idelalisib for multiple B-cell malignancies. This review\narticle focuses on the progress made in the discovery and\ndevelopment of novel PI3K inhibitors, with an emphasis on\nantitumour activity and tolerability profiles for agents that have\nentered clinical trials. We also discuss the key issues of drug\nresistance, patient selection approaches and rational targeted\ncombinations. Finally, we envision the future development and\nuse of PI3K inhibitors for the treatment of patients with a range of\nmalignancies.
Loading....