The phosphoinositide 3-kinase (PI3K) pathway, one of the most commonly activated signaling pathways in human cancers, plays a crucial role in the regulation of cell proliferation, differentiation, and survival. This pathway is usually activated by receptor tyrosine kinases (RTKs), whose constitutive and aberrant activation is via gain-of-function mutations, chromosomal rearrangement, gene amplification and autocrine. Blockage of PI3K pathway by targeted therapy on RTKs with tyrosine kinases inhibitors (TKIs) and monoclonal antibodies (mAbs) has achieved great progress in past decades; however, there still remain big challenges during their clinical application. In this review, we provide an overview about the most frequently encountered alterations in RTKs and focus on current therapeutic agents developed to counteract their aberrant functions, accompanied with discussions of two major challenges to the RTKs-targeted therapy in cancer – resistance and toxicity.

磷酸肌醇3-激酶（PI3K）途径，在人类癌症中最常被激活的信号传导途径之一，在调节细胞增殖，分化和存活中起着至关重要的作用。该途径通常由受体酪氨酸激酶（RTKs）激活，其功能性激活是通过功能获得性突变，染色体重排，基因扩增和自分泌而进行的。在过去的几十年中，通过靶向治疗酪氨酸激酶抑制剂（TKI）和单克隆抗体（mAb）对RTK的阻断PI3K途径取得了巨大进展。但是，在临床应用中仍然存在很大的挑战。在这篇评论中，我们提供了有关RTK最常见变化的概述，并重点介绍了为抵消其异常功能而开发的当前治疗剂，