Saraon Punit, Pathmanathan Shivanthy, Snider Jamie, Lyakisheva Anna, Wong Victoria, Stagljar Igor
Drug Discovery Program, Ontario Institute for Cancer Research, Toronto, ON, Canada.
Donnelly Centre, University of Toronto, Toronto, ON, Canada.
Oncogene. 2021 Jun;40(24):4079-4093. doi: 10.1038/s41388-021-01841-2. Epub 2021 Jun 2.
Receptor tyrosine kinases (RTKs) are transmembrane receptors of great clinical interest due to their role in disease, notably cancer. Since their discovery, several mechanisms of RTK dysregulation have been identified, resulting in multiple cancer types displaying 'oncogenic addiction' to RTKs. As a result, RTKs have represented a major class for targeted therapeutics over the past two decades, with numerous small molecule-based tyrosine kinase inhibitor (TKI) therapeutics having been developed and clinically approved for several cancers. However, many of the current RTK inhibitor treatments eventually result in the rapid development of acquired resistance and subsequent tumor relapse. Recent technological advances and tools are being generated for the identification of novel RTK small molecule therapeutics. These newer technologies will be important for the identification of diverse types of RTK inhibitors, targeting both the receptors themselves as well as key cellular factors that play important roles in the RTK signaling cascade.
受体酪氨酸激酶（RTK）是一类跨膜受体，因其在疾病尤其是癌症中的作用而备受临床关注。自发现以来，已确定了几种RTK失调机制，导致多种癌症类型对RTK表现出“致癌成瘾”。因此，在过去二十年中，RTK一直是靶向治疗的主要类别，已经开发出许多基于小分子的酪氨酸激酶抑制剂（TKI）疗法，并在临床上被批准用于多种癌症。然而，目前许多RTK抑制剂治疗最终都会导致获得性耐药的快速发展和随后的肿瘤复发。目前正在开发用于鉴定新型RTK小分子疗法的技术进展和工具。这些更新的技术对于鉴定不同类型的RTK抑制剂非常重要，这些抑制剂既靶向受体本身，也靶向在RTK信号级联中起重要作用的关键细胞因子。
