Small-Molecule Immuno-Oncology Therapy: Advances, Challenges and New Directions

doi:10.2174/1568026619666190308131805

	Small-Molecule Immuno-Oncology Therapy: Advances, Challenges and New Directions
	Chen, Shulun 1,2,3; Song, Zilan 1,2,3; Zhang, Ao 1,2,3
刊名	CURRENT TOPICS IN MEDICINAL CHEMISTRY
	2019
卷号	19 期号:3 页码:180-185
ISSN号	1568-0266
DOI	10.2174/1568026619666190308131805
通讯作者	Zhang, Ao(aozhang@simm.ac.cn)
英文摘要	Oncology immunotherapy has gained significant advances in recent years and benefits cancer patients with superior efficacy and superior clinical responses. Currently over ten immune checkpoint antibodies targeting CTLA-4 and PD-1/PD-L1 have received regulatory approval worldwide and over thousands are under active clinical trials. However, compared to the rapid advance of Monoclonal Antibody (mAb), studies on immunotherapeutic small molecules have far lagged behind. Small molecule immunotherapy not only can target immunosuppressive mechanisms similar to mAbs, but also can stimulate intracellular pathways downstream of checkpoint proteins in innate or adaptive immune cells that mAbs are unable to access. Therefore, small molecule immunotherapy can provide an alternative treatment modality either alone or complementary to or synergistic with extracellular checkpoint mAbs to address low clinical response and drug resistance. Fortunately, remarkable progress has achieved recently in the pursuit of small molecule immunotherapy. This review intends to provide a timely highlight on those clinically investigated small molecules targeting PD-1/PD-L1, IDO1, and STING. The most advanced IDO1 inhibitor epacadostat have been aggressively progressed into multiple clinical testings. Small molecule PD-1/PD-L1 inhibitors and STING activators are still in a premature state and their decisive application needs to wait for the ongoing clinical outcomes. Since no small molecule immunotherapy has been approved yet, the future research should continue to focus on discovery of novel small molecules with distinct chemo-types and higher potency, identification of biomarkers to precisely stratify patients, as well as validation of many other immune-therapeutic targets, such as LAG3, KIRs, TIM-3, VISTA, B7-H3, and TIGIT.
资助项目	Chinese NSF[81773565] ; National Program on Key Basic Research Project of China[2015CB910603-004] ; Key Program of the Frontier Science of the Chinese Academy of Sciences[160621] ; Shanghai Commission of Science and Technology[16XD1404600] ; Strategic Leading Project A on Precision Medicine of the Chinese Academy of Sciences[XDA12020366] ; Strategic Leading Project A on Precision Medicine of the Chinese Academy of Sciences[XDA12020226]
WOS关键词	PEMBROLIZUMAB
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	BENTHAM SCIENCE PUBL LTD
WOS记录号	WOS:000464102200003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/290094]
专题	中国科学院上海药物研究所
通讯作者	Zhang, Ao
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, SIMM, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, SIMM, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Chen, Shulun,Song, Zilan,Zhang, Ao. Small-Molecule Immuno-Oncology Therapy: Advances, Challenges and New Directions[J]. CURRENT TOPICS IN MEDICINAL CHEMISTRY,2019,19(3):180-185.
APA	Chen, Shulun,Song, Zilan,&Zhang, Ao.(2019).Small-Molecule Immuno-Oncology Therapy: Advances, Challenges and New Directions.CURRENT TOPICS IN MEDICINAL CHEMISTRY,19(3),180-185.
MLA	Chen, Shulun,et al."Small-Molecule Immuno-Oncology Therapy: Advances, Challenges and New Directions".CURRENT TOPICS IN MEDICINAL CHEMISTRY 19.3(2019):180-185.