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

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.

Computational analysis of morphological and molecular features in gastric cancer tissues

“…1,2 These components systematically orchestrate and dynamically change in a variety of disease states such as cancer. 3,4 Characteristics of cancerous tissues derived from patients provides diagnostic information regarding the tumors, and allows prediction of therapeutic responses 5,6 and prognosis. [7][8][9] Pathological assessment of cancer specimens stained with hematoxylin and eosin (H&E) is primarily interpreted not only by tissue architecture but also by nuclear morphology of the tumor cells, which has been used for routine clinical diagnosis 4,10 and computer-aided pathological diagnosis.…”

The roles of PD‐1/PD‐L1 and its signalling pathway in gastrointestinal tract cancers

“…Consistent with the abovementioned findings regarding PD‐1 and miR‐152, Gengchen Xie et al demonstrated that miR‐152 and miR‐200b targeted B7‐H1/PD‐1 mRNA and suppressed B7‐H1 expression in gastric cancer of patients infected with Hp . More importantly, PD‐1/PD‐L1 inhibitors as emerging therapeutic targets in gastric cancer have been gradually reviewed …”

Estimating Survival Probabilities of Advanced Gastric Cancer Patients in the Second-Line Setting: The Gastric Life Nomogram

“…No molecular biomarker is expected on the horizon in order to refine patient selection for both chemotherapy and antiangiogenic treatments. On the other side, other promising agents -among others several immune checkpoint inhibitors [23] and the VEGFR-2 inhibitor apatinib [24] -are almost ready to enter the therapeutic landscape of mGC. For instance, both the anti-PD1 monoclonal antibody nivolumab [25] and apatinib [26] conferred a significant OS gain over placebo in the third-line setting in Asian phase III trials.…”