Phosphoinositide 3-kinase (PI3K) signaling regulates cellular proliferation, survival and metabolism, and its aberrant activation is one of the most frequent oncogenic events across human cancers. In the last few decades, research has focused on the development of PI3K inhibitors, from preclinical tool compounds to the highly specific medicines approved to treat patients with cancer. Herein we discuss current paradigms for PI3K inhibitors in cancer therapy, focusing on clinical data and mechanisms of action. We also discuss current limitations in the use of PI3K inhibitors, including toxicities and mechanisms of resistance, with specific emphasis on approaches aimed at improving efficacy.

磷酸肌醇 3-激酶 (PI3K) 信号调节细胞增殖、存活和代谢，其异常激活是人类癌症中最常见的致癌事件之一。在过去的几十年里，研究一直集中在 PI3K 抑制剂的开发上，从临床前工具化合物到批准用于治疗癌症患者的高度特异性药物。在此我们讨论 PI3K 抑制剂在癌症治疗中的当前范例，重点是临床数据和作用机制。我们还讨论了目前使用 PI3K 抑制剂的局限性，包括毒性和耐药机制，特别强调旨在提高疗效的方法。