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Arora S , Velichinskii R , Lesh RW , Ali U , Kubiak M , Bansal P , Borghaei H , Edelman MJ , Boumber Y
Existing and Emerging Biomarkers for Immune Checkpoint Immunotherapy in Solid Tumors
Adv Ther. 2019 Aug 13;36(10) :2638-2678
PMID: 31410780    PMCID: PMC6778545    URL: https://www.ncbi.nlm.nih.gov/pubmed/31410780
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In the last few years, immunotherapy has transformed the way we treat solid tumors, including melanoma, lung, head neck, breast, renal, and bladder cancers. Durable responses and long-term survival benefit has been experienced by many cancer patients, with favorable toxicity profiles of immunotherapeutic agents relative to chemotherapy. Cures have become possible in some patients with metastatic disease. Additional approvals of immunotherapy drugs and in combination with other agents are anticipated in the near future. Multiple additional immunotherapy drugs are in earlier stages of clinical development, and their testing in additional tumor types is under way. Despite considerable early success and relatively fewer side effects, the majority of cancer patients do not respond to checkpoint inhibitors. Additionally, while the drugs are generally well tolerated, there is still the potential for significant, unpredictable and even fatal toxicity with these agents. Improved biomarkers may help to better select patients who are more likely to respond to these drugs. Two key biologically important predictive tissue biomarkers, specifically, PD-L1 and mismatch repair deficiency, have been FDA-approved in conjunction with the checkpoint inhibitor, pembrolizumab. Tumor mutation burden, another promising biomarker, is emerging in several tumor types, and may also soon receive approval. Finally, several other tissue and liquid biomarkers are emerging that could help guide single-agent immunotherapy and in combination with other agents. Of these, one promising investigational biomarker is alteration or deficiency in DNA damage response (DDR) pathways, with altered DDR observed in a broad spectrum of tumors. Here, we provide a critical overview of current, emerging, and investigational biomarkers in the context of response to immunotherapy in solid tumors.
1865-8652 Arora, Sanjeevani Velichinskii, Rodion Lesh, Randy W Ali, Usman Kubiak, Michal Bansal, Pranshu Borghaei, Hossein Edelman, Martin J Boumber, Yanis Journal Article Review United States Adv Ther. 2019 Aug 13. pii: 10.1007/s12325-019-01051-z. doi: 10.1007/s12325-019-01051-z.