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Gastrointest Cancer. 2017;7:1-11. doi: 10.2147/GICTT.S113525. Epub 2017 May 5.

PD-1 and PD-L1 as emerging therapeutic targets in gastric cancer: current evidence.

Author information

1
Division of Hematology-Oncology, University of California Irvine, Orange.
2
Department of Medical Oncology and Developmental Therapeutics, City of Hope, Duarte.
3
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center.
4
The Angeles Clinic and Research Institute, Los Angeles, CA, USA.

Abstract

Gastric adenocarcinoma is a leading cause of global cancer-related morbidity and mortality, and new therapeutic approaches are needed. Despite the improved outcomes with monoclonal antibodies targeting human epidermal growth factor receptor 2 and vascular endothelial growth factor receptor 2, durable responses are uncommon. Targeting immune checkpoints including PD-1, PD-L1 and CTLA-4 have led to improved survival across several tumor types, frequently characterized by prolonged benefit in responding patients. Tumoral and lymphocyte-derived immunohistochemical staining for PD-1, PD-L1, and tumor mutational burden have shown potential as predictive response biomarkers in several tumor types. Optimal incorporation of immune-mediated therapies into gastric cancer (GC) is an area of intense ongoing investigation and benefit has been demonstrated in smaller studies of advanced patients. Important questions of biomarker selection, roles for molecular characterization, optimal combinatorial approaches, and therapeutic sequencing remain. In this study, current data are reviewed for immune checkpoint inhibitors in GC, and putative biomarkers, ongoing trials, and future considerations are discussed.

KEYWORDS:

checkpoint inhibitor; immunotherapy; nivolumab; pembrolizumab; stomach cancer; tumor mutational burden

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