ABSTRACT

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer and is usually not diagnosed until an advanced-stage disease is present. Chemotherapy is the recommended treatment; however, it is known that chemotherapy alone has a low cure rate, harmful side effects, and a lack of sensitivity. Therefore, alternatives to improve the patient's experience and outcomes with immunotherapy are being used as first-line treatment in patients with NSCLC. Patients may develop primary or acquired resistance against immunotherapy, and the mechanisms of resistance are not yet fully understood. Currently, several new approaches are being developed to overcome immunotherapy resistance in NSCLC. Herein, we briefly discuss pathways driving resistance to immunotherapy and new alternatives that are being developed to overcome resistance.

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Competing Interests

Source of Support: Christian Rolfo: Lung Cancer Research Foundation-Pfizer Grant 2019, National Institute of Health (NIH) U54 grant (Project co-leader). Andrés F. Cardona: Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Foundation Medicine, Roche Diagnostics, Termo Fisher, Broad Institute, BioNTech, Amgen, Flatiron Health, Teva Pharma, Rochem Biocare, Bayer, INQBox and The Foundation for Clinical and Applied Cancer Research – FICMAC. Camila Ordóñez-Reyes: None.

Conflict of Interest: Christian Rolfo: Speaker for MSD, Astra Zeneca, Roche; advisory board for Inivata, ArcherDx, MD Serono, BMS, Novartis; research collaboration with GuardantHealth; educational committee member of International Association for the Study of Lung Cancer (IALSC), Vice President of International Society of Liquid Biopsy, educational Chair forOncology Latin American Association, faculty for American Society of Clinical Oncology (ASCO) International; and scientific committee member of European School of Oncology. Andrés F. Cardona: Advisor and speaker for EISAI, Merck Serono, Jannsen Pharmaceutical, Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Novartis, Celldex Therapeutics, Foundation Medicine, Eli Lilly, Guardant Health, Illumina, and Foundation for Clinical and Applied Cancer Research – FICMAC. Camila Ordóñez-Reyes: None.