Reprogramming paneth-like plasticity: FGFR3 as a key to overcoming KRAS-EGFR resistance in CRC

Abstract

Dual KRAS-epidermal growth factor receptor (EGFR) inhibition holds promise for KRAS-mutant colorectal cancer (CRC), yet drug resistance remains a key hurdle. This study by Zhang et al. identifies the SMAD family member 1 (SMAD1)-fibroblast growth factor receptor 3 (FGFR3) axis as the driver of Paneth-like lineage plasticity that mediates such resistance and demonstrates that FGFR3 targeting restores drug sensitivity and synergizes with dual pathway inhibition in preclinical models^[1].

Acknowledgments

This work is supported by the National Natural Science Foundation of China (Grant Nos 82573166, 82504847) and the Jiangsu Provincial Natural Science Foundation Youth Fund Project (Grant No. BK20251567).

Ethical statements

Not applicable.

Author contributions

The authors confirm contributions to the paper as follows: study conception and design: Yin Z, Guo X, Liu X; literature review: Yin Z, Guo X; draft manuscript preparation: Yin Z, Guo X. All authors reviewed the results and approved the final version of the manuscript.

Data availability

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Conflict of interest

The authors declare that they have no conflict of interest.

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