TY - JOUR
T1 - Targetable gene fusions and aberrations in genitourinary oncology
AU - Pederzoli, Filippo
AU - Bandini, Marco
AU - Marandino, Laura
AU - Ali, Siraj M.
AU - Madison, Russell
AU - Chung, Jon
AU - Ross, Jeffrey S.
AU - Necchi, Andrea
N1 - Publisher Copyright:
© 2020, Springer Nature Limited.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41585-020-00379-4
DO - 10.1038/s41585-020-00379-4
M3 - Review article
C2 - 33046892
AN - SCOPUS:85092370476
VL - 17
SP - 613
EP - 625
JO - Nature Reviews Urology
JF - Nature Reviews Urology
SN - 1759-4812
IS - 11
ER -