Functional and mechanistic studies on the transition from adenocarcinoma to squamous cell carcinoma in lung cancer drug resistance
Journal Title: Biomedical Transformation - Year 2021, Vol 2, Issue 1
Abstract
Lung cancer, featured with strong heterogeneity and plasticity, is the most devastating disease worldwide. Based on histological classification, lung cancer can be categorized as small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), among which the latter could be further classified into lung adenocarcinoma (ADC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC). Mixed pathologies of ADC and SCC (Adenosquamous Cell Carcinoma, Ad-SCC) or mixed SCLC with ADC and/or SCC pathology (mixed SCLC) have been consistently observed in clinic. Lung Ad-SCC is about 4%~10% of NSCLC. Recent clinical studies have shown that epidermal growth factor receptor (EGFR) mutant lung ADC could transition to SCC in relapsed patients failed from chemotherapy, targeted therapy or immunotherapy. Studies of liver kinase B1 (Lkb1)-defi cient mouse model have provided convincing evidence in supporting that lung ADC derived from club cells or AT2 cells (Alveolar Epithelial Type 2 Cells) is prone to squamous transition, and the mixed AdSCC is identified as the intermediate stage. Mechanistic studies demonstrate that uncontrolled accumulation of excessive oxidative stress resulted from extracellular matrix depletion and metabolic reprogramming somehow triggers the up-regulation of SCC-lineage specific transcription factor, p63, which eventually promotes the squamous transition. Such transition confers lung tumors with drug resistance in mouse models. This review will summarize current research progress of the transition from lung ADC to SCC as well as its correlation with drug resistance acquisition, which hopefully provides novel insights into lung cancer plasticity and drug resistance.
Authors and Affiliations
ChenYueqing, ChenYuting, TongXinyuan, Ji Hongbin
Keywords
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- EP ID EP767191
- DOI 10.12287/j.issn.2096-8965.20210106
- Views 14
- Downloads 0
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