Targeting immune checkpoints in non small cell lung cancer


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Abstract

HighlightsOncogenic drivers and mechanisms of adaptive immunity are changing the landscape of lung cancer treatment.Cancers can disrupt cancer cell immune recognition by interfering with immune-check-point pathways.Immune check point molecules PD-1, PD-L1 and CTLA-4 are relevant targets for cancer therapy.Based on clinical trials, anti PD-1 and anti PD-L1 agents have been approved for advanced NSCL.Cancers have the ability to disrupt immune response by interfering with adaptive immunity. Blocking checkpoint pathways has become a target for pharmacological research in lung cancer with particular focus on peptides PD-1 and CTLA-4.A number of immune check-point inhibitors (ICIs) targeting both PD-1 and CTLA-4 pathways are under investigation within clinical trials, of which Nivolumab, Pembrolizumab and Atezolizumab have already been approved for lung cancer treatment by both FDA and EMA.Employed as single-agents in current practice for the treatment of advanced non-small cell lung cancer (NSCLC) ICIs have exhibited advantages in terms of overall survival and response rate with some responses being durable.Evaluating combinations of different inhibitors, dosing and sequencing within a multimodal therapy approach, together with better management of toxicity represents a new challenge for future research of therapy targeting immune check-points.

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