title: Small molecule drugs with immunomodulatory effects in cancer.
abstract: Immunotherapy shows promise for positively changing the landscape of the management of many advanced solid tumors, including gastrointestinal (GI) malignancies. Many of these developments have been focused on vaccine-based, monoclonal antibody therapies and more recently, checkpoint inhibitors, although many small molecule inhibitors can function as immunomodulators. Small molecule compounds have several advantages over conventional immunotherapeutic agents including: ease of production and the potential for oral administration. There is a potential niche for small molecule immunomodulators to enhance the efficacy of existing immunotherapeutic and cytotoxic agents. This article focuses on two categories of small molecule compounds with immunomodulatory effects: IDO and MEK inhibitors. Indoleamine -2, 3- dioxygenase (IDO) is known for its effects in tumor immunity. IDO inhibitors are generally well-tolerated and have the potential to enhance anti-tumor responses when combined with checkpoint inhibitors. MEK inhibitors affect signal transduction of the RAS-RAF-MEK pathway and numerous MEK inhibitors are currently being investigated in solid tumors. Small molecule immunomodulators are currently being investigated for their potential role in augmenting the effects of conventional immunotherapeutic agents although further research is required to identify those patients most likely to respond to combination therapy.
authors.affiliation: a The Bunting-Blaustein Cancer Research Building ; Baltimore , MD USA.
authors.forename: Adrian G
authors.initials: AG
authors.lastname: Murphy
authors.affiliation: a The Bunting-Blaustein Cancer Research Building ; Baltimore , MD USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000379:methods; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D020930:MAP Kinase Kinase Kinases
keywords: IDO inhibitors; MEK inhibitors; gastrointestinal malignancies; immunotherapy; small molecule