Molecular classification and precision therapy of cancer: immune checkpoint inhibitors

Abstract

On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body. FDA previously approved Keytruda for treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma, all of which carry positive programmed death-1/programmed death-ligand 1 biomarkers. Therefore, indications of Keytruda significantly expanded. Several types of malignancies are disclosed by MSI-H status due to dMMR and characterized by increased neoantigen load, which elicits intense host immune response in tumor microenvironment, including portions of colorectal and gastric carcinomas. Currently, biomarker-based patient selection remains a challenge. Pathologists play important roles in evaluating histology and biomarker results and establishing detection methods. Taking gastric cancer as an example, its molecular classification is built on genome abnormalities, but it lacks acceptable clinical characteristics. Pathologists are expected to act as “genetic interpreters” or “genetic translators” and build a link between molecular subtypes with tumor histological features. Subsequently, by using their findings, oncologists will carry out targeted therapy based on molecular classification.

Keywords

molecular classification / precision medicine / pembrolizumab / PD-1/PD-L1 / MSI-H

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Acknowledgements

The author would like to thank the Chinese National Key Program (Nos. 2017YFC0908303 and 2016YFC1303200), National Natural Science Foundation of China (Nos. 81772505 and 81372644), and Innovation Foundation of Translational Medicine of Shanghai Jiao Tong University School of Medicine (Nos. 15ZH1002, 15ZH4001, and TM201617) for supporting this study.

Compliance with ethics guidelines

Yingyan Yu declares no conflicts of interest. This article does not involve a research protocol requiring approval by a relevant institutional review board or ethics committee.

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2017 Higher Education Press and Springer-Verlag GmbH Germany