Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
Semin Cancer Biol. 2022 Nov;86(Pt 2):269-279. doi: 10.1016/j.semcancer.2022.07.001. Epub 2022 Jul 4.
Tumor microenvironment (TME) composes of multiple cell types and non-cellular components, which supports the proliferation, metastasis and immune surveillance evasion of tumor cells, as well as accounts for the resistance to therapies. Therefore, therapeutic strategies using small molecule inhibitors (SMIs) and antibodies to block potential targets in TME are practical for cancer treatment. Targeted protein degradation using PROteolysis-TArgeting Chimera (PROTAC) technic has several advantages over traditional SMIs and antibodies, including overcoming drug resistance. Thus many PROTACs are currently under development for cancer treatment. In this review, we summarize the recent progress of PROTAC development that target TME pathways and propose the potential direction of future PROTAC technique to advance as novel cancer treatment options.
肿瘤微环境（TME）由多种细胞类型和非细胞成分组成，它支持肿瘤细胞的增殖、转移和免疫逃避，也导致了对治疗的抵抗。因此，使用小分子抑制剂（SMIs）和抗体来阻断 TME 中潜在靶点的治疗策略在癌症治疗中是切实可行的。使用蛋白水解靶向嵌合体（PROTAC）技术进行靶向蛋白降解相对于传统的 SMIs 和抗体具有几个优势，包括克服耐药性。因此，目前有许多 PROTAC 正在开发用于癌症治疗。在这篇综述中，我们总结了靶向 TME 途径的 PROTAC 开发的最新进展，并提出了未来 PROTAC 技术的潜在发展方向，以作为新型癌症治疗选择。
