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Toward personalized treatment approaches for non-small-cell lung cancer

Abstract

Worldwide, lung cancer is the most common cause of cancer-related deaths. Molecular targeted therapies and immunotherapies for non-small-cell lung cancer (NSCLC) have improved outcomes markedly over the past two decades. However, the vast majority of advanced NSCLCs become resistant to current treatments and eventually progress. In this Perspective, we discuss some of the recent breakthrough therapies developed for NSCLC, focusing on immunotherapies and targeted therapies. We highlight our current understanding of mechanisms of resistance and the importance of incorporating genomic analyses into clinical studies to decipher these further. We underscore the future role of neoadjuvant and maintenance combination therapy approaches to potentially cure early disease. A major challenge to successful development of rational combination therapies will be the application of robust predictive biomarkers for clear-cut patient stratification, and we provide our views on clinical research areas that could influence how NSCLC will be managed over the coming decade.

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Fig. 1: Molecular landscape of NSCLC.
Fig. 2: Illustration of OS for targeted and immunochemotherapy approaches.
Fig. 3: Major mechanisms of secondary immune escape to ICBs.

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M.W., R.S.H. and C.B. conceived, wrote and edited this review.

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Correspondence to Roy S. Herbst or Chris Boshoff.

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R.S.H. receives consulting fees from Abbvie Pharmaceuticals, ARMO Biosciences, AstraZeneca, Bayer HealthCare Pharmaceuticals, Bolt Biotherapeutics, Bristol-Myers Squibb, Candel Therapeutics, Cybrexa Therapeutics, eFFECTOR Therapeutics, Eli Lilly and Company, EMD Serono, Foundation Medicine, Genentech and Roche, Genmab, Gilead, Halozyme Therapeutics, Heat Biologics, I-Mab Biopharma, Immunocore, Infinity Pharmaceuticals, Loxo Oncology, Merck, Mirati Therapeutics, Nektar, Neon Therapeutics, NextCure, Novartis, Ocean Biomedical, Oncternal Therapeutics, Pfizer, Refactor Health, Ribbon Therapeutics, Sanofi, Seattle Genetics, Shire PLC, Spectrum Pharmaceuticals, STCubePharmaceuticals, Symphogen, Takeda, Tesaro, Tocagen, Ventana Medical Systems, WindMIL Therapeutics, Xencor. R.S.H. also receives research support from AstraZeneca, Eli Lilly and Company, Genentech and Roche, and Merck, and serves as a board member (non-executive, independent member) for Immunocore Holdings and Junshi Pharmaceuticals. C.B. is an employee and shareholder of Pfizer. M.W. declares no competing interests.

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Wang, M., Herbst, R.S. & Boshoff, C. Toward personalized treatment approaches for non-small-cell lung cancer. Nat Med 27, 1345–1356 (2021). https://doi.org/10.1038/s41591-021-01450-2

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