FGFR blockade by pemigatinib treats naïve and castration resistant prostate cancer

Paola Chiodelli, Daniela Coltrini, Marta Turati, Marianna Cerasuolo, Federica Maccarinelli, Sara Rezzola, Elisabetta Grillo, Arianna Giacomini, Sara Taranto, Silvia Mussi, Alessia Ligresti, Marco Presta, Roberto Ronca*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Prostate cancer (PCa) is a leading cause of cancer mortality in the male population commonly treated with androgen deprivation therapy (ADT) and relapsing as aggressive and androgen-independent castration-resistant prostate cancer (CRPC). In PCa the FGF/FGFR family of growth factors and receptors represents a relevant mediator of cancer growth, tumor-stroma interaction, and a driver of resistance and relapse to ADT.

In the present work, we validate the therapeutic efficacy the FDA-approved FGFR inhibitor pemigatinib, in an integrated platform consisting of human and murine PCa cells, and the transgenic multistage TRAMP model of PCa that recapitulates both androgen-dependent and CRPC settings. Our results show for the first time that pemigatinib causes intracellular stress and cell death in PCa cells and prevents tumor growth in vivo and in the multistage model. In addition, the combination of pemigatinib with enzalutamide resulted in long-lasting tumor inhibition and prevention of CRPC relapse in TRAMP mice. These data are confirmed by the implementation of a stochastic mathematical model and in silico simulation.

Pemigatinib represents a promising FDA-approved FGFR inhibitor for the treatment of PCa and CRPC alone and in combination with enzalutamide.
Original languageEnglish
JournalCancer Letters
Early online date1 Dec 2021
DOIs
Publication statusEarly online - 1 Dec 2021

Keywords

  • FGFR inhibitor
  • pemigatinib
  • Prostate cancer
  • castrate resistant prostate cancer
  • TRAMP
  • mathematical model

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