Toxicity Mechanism and Clinical features of PD-1/PD-L1 Inhibitors in Treatment of Cancer, Volume II

This Research Topic is part of a series with:

Toxicity Mechanism and Clinical features of PD-1/PD-L1 Inhibitors in Treatment of Cancer, Volume I

PD-1 and PD-L1 inhibitors are important targets in immunotherapy for cancer treatment. Anti-PD-1/PD-L1 antibodies have been developed to combat many cancers as a result of their success compared to conventional cancer treatment with monoclonal antibodies. There has been a total paradigm shift in the treatment of oncological malignancies as more anti-PD-1/PD-L1 agents have also been approved by the FDA (US) and the European Medicines Agency (EMA).

The increase in anti-PD-1/PD-L1 agents use has provoked the emergence of a new spectrum of toxicities. These toxicities depend on the individual patient and the specific type of anti-PD-1/PD-L1 agent used in the treatment. The incidence of fatal cancer immunotherapy associated toxicities is estimated to be between 0.3% and 1.3%. Numerous clinical trials and studies have investigated the treatment-related toxicities of PD-1 and PD-L1 inhibitors. However, further research is required to fully understand the mechanism of these toxicities.

Monoclonal antibodies have been used to address this challenge as they can act as antagonists in the PD-1/PD-L1 signalling pathway but there are still several inherent limitations with this. Thus, there is the need for small molecular inhibitors with the ability to directly block PD-1/PD-L1 or inhibit the translation of PD-L1 by promoting the degradation of PD-L1. Furthermore, the druggability of these small molecule inhibitors must be carefully assessed. This is very important for the success of PD-1/PD-L1 based cancer immunotherapy.

The aim of this Research Topic is to explore the mechanism of pharmacological toxicity induced by PD-1/ PD-L1 inhibitors and explore the difference in the incidence of toxicities between patients treated with PD-1 or PD-L1 inhibitors and those treated without. We welcome submission including but not limited to:

• Original Research on the mechanism of pharmacological toxicity induced by PD-1/ PD-L1 inhibitors in all tissues as well as those in the event of treatment leading to discontinuation.

• Original Research investigating the clinical features of PD-1/ PD-L1 inhibitors’ toxicities

•Studies on single drug toxicities and treatment with PD-1/PD-L1 inhibitors combined with chemotherapy in clinical practice.

• Systematic review and meta-analysis of toxicities of PD-1/ PD-L1 inhibitors in treatment of cancer including single toxicity or multiple toxicities in different systems.

Keywords: immune-checkpoint inhibitors, PD-1/PD-L1 inhibitors, toxicity, clinical features, cancer

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