Emerging horizons in cancer therapy: Squamous transition drives drug resistance

TL;DR

Cancer cells can change into squamous-like cells, making them resistant to certain drugs, and this transition is a key factor in treatment failure.

Contribution

The paper highlights adeno-to-squamous transition (AST) as a novel mechanism of drug resistance in lung cancer.

Findings

Adeno-to-squamous transition (AST) is linked to resistance to KRAS inhibitors in non-small cell lung cancer.

Expression of KRT6A in adenocarcinoma correlates with poor response to KRAS inhibitors.

Abstract

Adeno‐to‐squamous transition (AST) has emerged as a driver of targeted therapy resistance. Studies of KRAS/LKB1‐mutant non‐small cell lung cancer (NSCLC) have revealed the progressive acquisition of squamous signatures during treatment with KRAS inhibitors, ultimately inducing drug resistance. Moreover, the expression of squamous‐related gene KRT6A in adenocarcinoma (ADC) correlates with poor responses to KRAS inhibitors. In this commentary, we discuss the role of AST in drug resistance and propose future directions to elucidate the underlying mechanisms.

Adeno‐to‐squamous transition (AST) drives targeted therapy resistance.Progressive plasticity is acquired during Adeno‐to‐squamous transition (AST).

Adeno‐to‐squamous transition (AST) drives targeted therapy resistance.

Progressive plasticity is acquired during Adeno‐to‐squamous transition (AST).

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