Small molecule-based immunomodulators for cancer therapy

作者：Yinrong Wu, Zichao Yang, Kui Cheng, Huichang Bi, Jianjun Chen · 发表于：Acta Pharmaceutica Sinica B · 年份：2022 · DOI：10.1016/j.apsb.2022.11.007 · 被引用次数：107 · 研究领域：Nanoplatforms for cancer theranostics、Cancer Research and Treatments、Cancer Immunotherapy and Biomarkers

., specificity and efficacy). However, they have limitations in terms of pharmacokinetics including long half-lives, poor tissue/tumor penetration, and little/no oral bioavailability. In addition, therapeutic antibodies are immunogenic, thus may cause unwanted adverse effects. Therefore, researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy, as small molecules may overcome the above disadvantages associated with antibodies. Further, small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment, and may be combined to elicit synergistic effects. Recent years have witnessed the rapid development of small molecule-based cancer immunotherapy. In this review, we describe the current progress in small molecule-based immunomodulators (inhibitors/agonists/degraders) for cancer therapy, including those targeting PD-1/PD-L1, chemokine receptors, stimulator of interferon genes (STING), Toll-like receptor (TLR), etc. The tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized.