Therapeutic targeting of immune checkpoints with small molecule inhibitors

American Journal of Translational Research

Wade M Smith¹  Collin M Labak²  Colin N Bomstad³  Ian J Purvis⁴  Kiran K Velpula⁵ 

[1] Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL;Department of Health Sciences Education, University of Illinois College of Medicine, Peoria, IL;Department of Illinois Neurological Institute, University of Illinois College of Medicine, Peoria, IL;Department of Neurosurgery, University of Illinois College of Medicine, Peoria, IL;Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO

关键词: Small molecule inhibitors;    immune checkpoints;    cancer progression;    epigenetics;    tumor microenvironment;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Immune checkpoints are known to contribute to tumor progression by enhancing cancer’s ability to evade the immune system and metastasize. Immunotherapies, including monoclonal antibodies, have been developed to target specific immunosuppressive molecules on the membranes of cancer cells and have proven revolutionary in the field of oncology. Recently, small molecule inhibitors (SMIs) have gained increased attention in cancer research with potential applications in immunotherapy. SMIs have desirable benefits over large-molecule inhibitors, such as monoclonal antibodies, including greater cell permeability, organ specificity, longer half-lives, cheaper production costs, and the possibility for oral administration. This paper will review the mechanisms by which noteworthy and novel immune checkpoints contribute to tumor progression, and how they may be targeted by SMIs and epigenetic modifiers to offer possible adjuvants to established therapeutic regimens. SMIs target immune checkpoints in several ways, such as blocking signaling between tumorigenic factors, building immune tolerance, and direct inhibition via epigenetic repression of immune inhibitory molecules. Further investigation into combination therapies utilizing SMIs and conventional cancer therapies will uncover new treatment options that may provide better patient outcomes across a range of cancers.

【 授权许可】

CC BY-NC