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Programmed death receptor-1/programmed death-ligand 1 inhibitors: Clinical progress and biomarker exploration in
Jin Shi1,2, Xudong Song3, Zihao Gao3
1Department of Pediatric Surgery, University Children's Hospital Basel, 4031, Basel, Switzerland.
Abstract:
Gastric cancer is one of the most common malignant tumours, with limited treatment options and poor prognosis in its advanced stages. In recent years, breakthroughs in tumour immunotherapy have led to immune checkpoint inhibitors becoming a new class of clinical oncology drugs. Programmed death receptor-1 (PD-1) and programmed death-ligand 1 (PD-L1) play significant roles in inhibiting T cell responses and tumour immune escape. PD-1/PD-L1 inhibitors can significantly improve the prognosis of patients with advanced gastric cancer. Moreover, the combination of administering PD-1/PD-L1 inhibitors along with chemotherapy, radiotherapy, targeted therapy, and other immunotherapies may further enhance therapeutic efficacy. However, some scientific issues need to be urgently resolved in the immunotherapy of gastric cancer, including the suboptimal efficacy of PD-1/PD-L1 inhibitor monotherapy, high incidence of immune-related adverse events, and the absence of definitive biomarkers for effectively screening treatment-sensitive populations. This article reviews the mechanism of action, therapeutic advances, adverse effects, and putative predictive biomarkers of PD-1/PD-L1 inhibitors in the treatment of advanced gastric cancer.
Insights
Immune checkpoint inhibitors targeting programmed death receptor-1 (PD-1) and programmed death-ligand 1 (PD-L1) show promise for advanced gastric cancer. Further research is needed to optimize efficacy and identify predictive biomarkers.
Area of Science:
- Oncology
- Immunotherapy
- Gastroenterology
Background:
- Gastric cancer is a leading cause of cancer death with limited advanced-stage treatment options.
- Tumor immunotherapy, specifically immune checkpoint inhibitors, has emerged as a significant advancement.
- Programmed death receptor-1 (PD-1) and programmed death-ligand 1 (PD-L1) are crucial in T-cell inhibition and tumor immune evasion.
Purpose of the Study:
- To review the mechanism of action, therapeutic progress, and adverse effects of PD-1/PD-L1 inhibitors in advanced gastric cancer.
- To discuss current challenges, including suboptimal monotherapy efficacy and the need for predictive biomarkers.
- To explore potential combination therapies to enhance treatment outcomes.
Main Methods:
- Review of current literature on PD-1/PD-L1 inhibitors in gastric cancer treatment.
- Analysis of mechanisms of action, clinical efficacy, and safety profiles.
- Identification and discussion of potential predictive biomarkers for patient selection.
Main Results:
- PD-1/PD-L1 inhibitors can improve prognosis in advanced gastric cancer patients.
- Combination therapies (chemotherapy, radiotherapy, targeted therapy, other immunotherapies) may enhance efficacy.
- Challenges remain, including limited monotherapy effectiveness, immune-related adverse events, and lack of definitive biomarkers.
Conclusions:
- PD-1/PD-L1 inhibitors represent a promising therapeutic strategy for advanced gastric cancer.
- Further research is essential to overcome current limitations and optimize patient selection through reliable biomarkers.
- Combination strategies hold potential for improved therapeutic benefits in gastric cancer immunotherapy.
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