Therapeutic targeting of immune checkpoints with small molecule inhibitors

Autor: Wade M, Smith, Ian J, Purvis, Colin N, Bomstad, Collin M, Labak, Kiran K, Velpula, Andrew J, Tsung, Jenna N, Regan, Sujatha, Venkataraman, Rajeev, Vibhakar, Swapna, Asuthkar
Rok vydání: 2018
Předmět:
Zdroj: American journal of translational research. 11(2)
ISSN: 1943-8141
Popis: 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.
Databáze: OpenAIRE