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2015 ; 11
(10
): 2463-8
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Small molecule drugs with immunomodulatory effects in cancer
#MMPMID26110550
Murphy AG
; Zheng L
Hum Vaccin Immunother
2015[]; 11
(10
): 2463-8
PMID26110550
show ga
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.