Abstract
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.
Original language | English (US) |
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Pages (from-to) | 2638-2678 |
Number of pages | 41 |
Journal | Advances in Therapy |
Volume | 36 |
Issue number | 10 |
DOIs | |
State | Published - Oct 1 2019 |
Funding
No funding or sponsorship was received for this study or publication of this article. Yanis Boumber was supported by the NIH R01 CA218802, NIH R21 CA223394 grants, and V Foundation translation award program T2018-013. Sanjeevani Arora was supported by the DOD W81XWH-18-1-0148. Martin Edelman was supported by the DOD W81XWH-18-1-0196 grant. Randy W. Lesh was supported by an Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship. All Fox Chase Cancer affiliated authors are in part supported by the NCI Core Grant, P30 CA006927, to Fox Chase Cancer Center. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Yanis Boumber has served on advisory boards of Astra Zeneca, AbbVie, and Caris Life Sciences. Hossein Borghaei has received research support for clinical trials from Millennium, Merck/Celgene, BMS/Lilly, has served on advisory board or as a consultant for BMS, Lilly, Genentech, Celgene, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, Astra Zeneca, Novartis, Genmab, Regeneron, BioNTech, Cantargia AB, Amgen, Abbvie, Axiom, PharmaMar, and on data and safety monitoring board for the University of Pennsylvania, CAR T Program. Martin J. Edelman has served on scientific advisory board for Biomarker strategies, as an advisor for Windmil Therapeutics, Syndax, on advisory boards for Armo, Bergen; data safety monitoring boards for Astra-Zeneca, Takeda, Boehringer Ingelheim and has received research funding from Apexigen, BMS, Nektar, Precision Oncology, and Merck. Sanjeevani Arora, Rodion Velichinskii, Randy W. Lesh, Usman Ali, Michal Kubiak, and Pranshu Bansal have nothing to disclose. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. No funding or sponsorship was received for this study or publication of this article. Yanis Boumber was supported by the NIH R01 CA218802, NIH R21 CA223394 grants, and V Foundation translation award program T2018-013. Sanjeevani Arora was supported by the DOD W81XWH-18-1-0148. Martin Edelman was supported by the DOD W81XWH-18-1-0196 grant. Randy W. Lesh was supported by an Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship. All Fox Chase Cancer affiliated authors are in part supported by the NCI Core Grant, P30 CA006927, to Fox Chase Cancer Center.
Keywords
- Biomarkers
- Cytotoxic T-lymphocyte antigen 4 (CTLA-4)
- DNA damage response (DDR)
- Immunotherapy
- Mismatch repair deficiency (MMR)
- Programmed death 1 (PD-1)
- Tumor mutation burden (TMB)
ASJC Scopus subject areas
- Pharmacology (medical)