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Review
. 2024 Jun 18:30:1611817.
doi: 10.3389/pore.2024.1611817. eCollection 2024.

Advancing neoadjuvant therapies in resectable non-small cell lung cancer: implications for novel treatment strategies and biomarker discovery

Hyein Jeon  1 , Rajvi Gor  2 , Angelica D'Aiello  1 , Brendon Stiles  3 , Peter B Illei  4 , Balazs Halmos  1
Affiliations
Review

Advancing neoadjuvant therapies in resectable non-small cell lung cancer: implications for novel treatment strategies and biomarker discovery

Hyein Jeon et al. Pathol Oncol Res. .

Abstract

The delivery of neoadjuvant and perioperative therapies for non-small cell lung cancer has been radically altered by significant advances and by the incorporation of targeted therapies as well as immune checkpoint inhibitors alone or alongside conventional chemotherapy. This evolution has been particularly notable in the incorporation of immunotherapy and targeted therapy into the treatment of resectable NSCLC, where recent FDA approvals of drugs such as nivolumab and pembrolizumab, in combination with platinum doublet chemotherapy, have led to considerable improvements in pathological complete response rates and the potential for enhanced long-term survival outcomes. This review emphasizes the growing importance of biomarkers in optimizing treatment selection and explores the impact of emerging studies that challenge existing treatment paradigms and investigate novel therapeutic combinations poised to redefine standard of care practices. Furthermore, the discussion extends to the unmet needs within perioperative treatment assessment and prognostication, highlighting the prospective value of biomarkers in evaluating treatment responses and prognosis.

Keywords: NSCLC; adjuvant; lung cancer; neoadjuvant; perioperative.

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Conflict of interest statement

BH—Receives clinical research funding from Boehringer Ingelheim, Astra Zeneca, Merck, BMS, Advaxis, Amgen, AbbVie, Daiichi, Pfizer, GSK, Beigene, Janssen, Black Diamond Therapeutics, Forward Pharma, Numab, Arrivent. Receives Honoraria from Astra Zeneca, Boehringer Ingelheim, Apollomics, Janssen, Takeda, Merck, BMS, Genentech, Pfizer, Eli-Lilly, Arcus, Merus, Daiichi, Precede. BS—Provides consulting and serves as advisory boards for Medtronic, AstraZeneca, Roche-Genentech, Pfizer, Arcus Biosciences, Bristol Myers Squib, Merck, Regeneron, Galvanize Therapeutics. Receives research funding from BMS Foundation and his wife owns salary/stock for SIGA Technologies. PI—Serves as advisory board for Agilent, AstraZeneca, Sanofi, AbbVie, Genentech, Merus, and speaks for Eli Lilly. Receives research funding from Bristol Myers-Squib. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Biomarkers for NSCLC. ctDNA, circulating tumor DNA; dMMR, mismatch repair deficient; IFNγ, interferon-gamma; KEAP1, Kelch-like ECH-associated protein 1; KRAS, Kirsten ras sarcoma oncogene; MSI, microsatellite instability; RB1, retinoblastoma 1 gene; STK11, serine/threonine kinase 11; TIL, tumor infiltrating lymphocytes; TMB, tumor mutation burden; TPS, tumor proportion score.
FIGURE 2
FIGURE 2
Key biomarkers for enhanced management and trial enrichment. ctDNA, circulating tumor DNA; mPR, major pathological response; MRD, minimal residual disease; NGS, next-generation sequencing; pCR, pathologic complete response; TIL, tumor infiltrating lymphocytes; TMB, tumor mutation burden.
See this image and copyright information in PMC

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