The FGF/FGFR signalling mediated anti-cancer drug resistance and therapeutic intervention

ABSTRACT 

Fibroblast Growth Factor (FGF) ligands and their receptors are crucial factors driving chemoresistance in several malignancies, challenging the efficacy of currently available anti-cancer drugs. The Fibroblast growth factor/receptor (FGF/FGFR) signalling malfunctions in tumor cells, resulting in a range of molecular pathways that may impact its drug effectiveness. Deregulation of cell signalling is critical since it can enhance tumor growth and metastasis. Overexpression and mutation of FGF/FGFR induce regulatory changes in the signalling pathways. Chromosomal translocation facilitating FGFR fusion production aggravates drug resistance. Apoptosis is inhibited by FGFR-activated signalling pathways, reducing multiple anti-cancer medications’ destructive impacts. Angiogenesis and epithelial-mesenchymal transition (EMT) are facilitated by FGFRs-dependent signalling, which correlates with drug resistance and enhances metastasis. Further, lysosome-mediated drug sequestration is another prominent method of resistance. Inhibition of FGF/FGFR by following a plethora of therapeutic approaches such as covalent and multitarget inhibitors, ligand traps, monoclonal antibodies, recombinant FGFs, combination therapy, and targeting lysosomes and micro RNAs would be helpful. As a result, FGF/FGFR suppression treatment options are evolving nowadays. To increase positive impacts, the processes underpinning the FGF/FGFR axis’ role in developing drug resistance need to be clarified, emphasizing the need for more studies to develop novel therapeutic options to address this significant problem. 

Communicated by Ramaswamy H. Sarma

Keywords:

• FGF/FGFR signalling
• chemoresistance
• anti-cancer drugs
• therapeutic approaches

Acknowledgments

SM, SK, and KDU acknowledge the Department of Biotechnology (DBT), University Grant Commission (UGC), and Department of Science and Technology (DST), Govt. of India, for providing a doctoral scheme under the JRF scheme.

Authors’ contributions

All authors contributed to the conception and design of the study. SM prepared the manuscript with the help of NAJ, SK, and KDU. PK supervised the study and edited the manuscript. All authors approved the final version of the manuscript for publication.

Disclosure statement

The authors declare that there is no conflict of interest.

Additional information

Funding

This work was supported by the Department of Science and Technology (DST), Govt. of India (grant number DST/NSM/R&D_HPC_Applications/2021/03.18).