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Theranostics 2019; 9(25):7849-7871. doi:10.7150/thno.37218 This issue Cite

Review

Small molecules as theranostic agents in cancer immunology

Jindian Li^1,2, Juno Van Valkenburgh¹, Xingfang Hong³, Peter S. Conti¹, Xianzhong Zhang^2✉, Kai Chen^1✉

1. Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC103, Los Angeles, CA 90033, USA.
2. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
3. Laboratory of Pathogen Biology, School of Basic Medical Sciences, Dali University, Dali 671000, China.

✉ Corresponding author: Dr. Xianzhong Zhang at the State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China; Tel and Fax: +86-592-2880645; E-mail: zhangxzhedu.cn; ORCID: 0000-0001-8591-8301. Dr. Kai Chen at the Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC103, Los Angeles, CA 90033, USA; Tel: +1 (323) 442-3858; Fax: +1 (323) 442-3253; E-mail: chenkaiusc.edu; ORCID: 0000-0002-8647-1182. More

Abstract

With further research into the molecular mechanisms and roles linking immune suppression and restraint of (pre)malignancies, immunotherapies have revolutionized clinical strategies in the treatment of cancer. However, nearly 70% of patients who received immune checkpoint therapeutics showed no response. Complementary and/or synergistic effects may occur when extracellular checkpoint antibody blockades combine with small molecules targeting intracellular signal pathways up/downstream of immune checkpoints or regulating the innate and adaptive immune response. After radiolabeling with radionuclides, small molecules can also be used for estimating treatment efficacy of immune checkpoint blockades. This review not only highlights some significant intracellular pathways and immune-related targets such as the kynurenine pathway, purinergic signaling, the kinase signaling axis, chemokines, etc., but also summarizes some attractive and potentially immunosuppression-related small molecule agents, which may be synergistic with extracellular immune checkpoint blockade. In addition, opportunities for small molecule-based theranostics in cancer immunology will be discussed.

Keywords: small molecules, theranostic agents, cancer immunology, molecular imaging, targeted therapy

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