Cell-by-Cell: Unlocking Lung Cancer Pathogenesis

Abstract

For lung cancers, cellular trajectories and fates are strongly pruned by cell intrinsic and extrinsic factors. Over the past couple of decades, the combination of comprehensive molecular and genomic approaches, as well as the use of relevant pre-clinical models, enhanced micro-dissection techniques, profiling of rare preneoplastic lesions and surrounding tissues, as well as multi-region tumor sequencing, have all provided in-depth insights into the early biology and evolution of lung cancers. The advent of single-cell sequencing technologies has revolutionized our ability to interrogate these same models, tissues, and cohorts at an unprecedented resolution. Single-cell tracking of lung cancer pathogenesis is now transforming our understanding of the roles and consequences of epithelial-microenvironmental cues and crosstalk during disease evolution. By focusing on non-small lung cancers, specifically lung adenocarcinoma subtype, this review aims to summarize our knowledge base of tumor cells-of-origin and tumor–immune dynamics that have been primarily fueled by single-cell analysis of lung adenocarcinoma specimens at various stages of disease pathogenesis and of relevant animal models. The review will provide an overview of how recent reports are rewriting the mechanistic details of lineage plasticity and intra-tumor heterogeneity at a magnified scale thanks to single-cell studies of early- to late-stage lung adenocarcinomas. Future advances in single-cell technologies, coupled with analysis of minute amounts of rare clinical tissues and novel animal models, are anticipated to help transform our understanding of how diverse micro-events elicit macro-scale consequences, and thus to significantly advance how basic genomic and molecular knowledge of lung cancer evolution can be translated into successful targets for early detection and prevention of this lethal disease.

Salvianolic acid B from Salvia miltiorrhiza bunge: A potential antitumor agent

“…Non-small cell lung cancer (NSCLC) is the most prevalent and aggressive type of lung cancer (Broderick, 2020) and comprises three main subtypes, large cell lung carcinoma, squamous cell lung Frontiers in Pharmacology frontiersin.org carcinoma, and adenocarcinoma (Babuta et al, 2022;Oronsky et al, 2022). Currently, small molecule TKIs and immunotherapy are among the first-line treatments for NSCLC that have improved survival rates in some patients (Koulouris et al, 2022;Sinjab et al, 2022). However, the overall mortality and morbidity of NSCLC patients remain high, especially in advanced stages.…”

The Third Joint Meeting on Lung Cancer of the FHU OncoAge (University Côte d’Azur, Nice, France) and the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Understanding New Therapeutic Options and Promising Predictive Biomarkers for Lung Cancer Patients

“…In this Special Issue, we have brought together several articles focusing on recent topics related to lung cancer in the fields of fundamental, translational, and clinical research [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Basic research studies are essential to improve our knowledge of lung cancer carcinogenesis.…”

“…Basic research studies are essential to improve our knowledge of lung cancer carcinogenesis. Therefore, discoveries from these basic studies can help to develop future therapeutics or new diagnostics, prognostics, or predictive biomarkers [ 5 , 8 , 11 , 12 ]. In particular, tissue and circulating biomarkers from the coding and non-coding regions of the genome that are predictive of the response or resistance to different immunotherapies or targeted therapies are currently being evaluated or used in clinical trials or, more recently, in daily practice [ 1 , 2 , 10 , 13 , 14 , 15 , 16 , 17 ].…”