Targetable gene fusions and aberrations in genitourinary oncology

Filippo Pederzoli, Marco Bandini, Laura Marandino, Siraj M. Ali, Russell Madison, Jon Chung, Jeffrey S. Ross, Andrea Necchi

Research output: Contribution to journalReview articlepeer-review


Gene fusions result from either structural chromosomal rearrangement or aberrations caused by splicing or transcriptional readthrough. The precise and distinctive presence of fusion genes in neoplastic tissues and their involvement in multiple pathways central to cancer development, growth and survival make them promising targets for personalized therapy. In genitourinary malignancies, rearrangements involving the E26 transformation-specific family of transcription factors have emerged as very frequent alterations in prostate cancer, especially the TMPRSS2–ERG fusion. In renal malignancies, Xp11 and t(6;11) translocations are hallmarks of a distinct pathological group of tumours described as microphthalmia-associated transcription factor family translocation-associated renal cell carcinomas. Novel druggable fusion events have been recognized in genitourinary malignancies, leading to the activation of several clinical trials. For instance, ALK-rearranged renal cell carcinomas have shown responses to alectinib and crizotinib. Erdafitinib has been tested for the treatment of FGFR-rearranged bladder cancer. Other anti-fibroblast growth factor receptor 3 (FGFR3) compounds are showing promising results in the treatment of bladder cancer, including infigratinib and pemigatinib, and all are currently in clinical trials.

Original languageEnglish
Pages (from-to)613-625
Number of pages13
JournalNature Reviews Urology
Issue number11
Publication statusPublished - Nov 1 2020

ASJC Scopus subject areas

  • Urology


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