Rogaratinib: A potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models

International Journal of Cancer. Journal International Du Cancer
Sylvia GrünewaldKarl Ziegelbauer

Abstract

Aberrant activation in fibroblast growth factor signaling has been implicated in the development of various cancers, including squamous cell lung cancer, squamous cell head and neck carcinoma, colorectal and bladder cancer. Thus, fibroblast growth factor receptors (FGFRs) present promising targets for novel cancer therapeutics. Here, we evaluated the activity of a novel pan-FGFR inhibitor, rogaratinib, in biochemical, cellular and in vivo efficacy studies in a variety of preclinical cancer models. In vitro kinase activity assays demonstrate that rogaratinib potently and selectively inhibits the activity of FGFRs 1, 2, 3 and 4. In line with this, rogaratinib reduced proliferation in FGFR-addicted cancer cell lines of various cancer types including lung, breast, colon and bladder cancer. FGFR and ERK phosphorylation interruption by rogaratinib treatment in several FGFR-amplified cell lines suggests that the anti-proliferative effects are mediated by FGFR/ERK pathway inhibition. Furthermore, rogaratinib exhibited strong in vivo efficacy in several cell line- and patient-derived xenograft models characterized by FGFR overexpression. The observed efficacy of rogaratinib strongly correlated with FGFR mRNA expression levels. These pro...Continue Reading

References

Oct 1, 1986·The Journal of Urology·H B GrossmanB Cox
May 17, 2001·Proceedings of the National Academy of Sciences of the United States of America·S H OngI Lax
Jan 19, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Astrid LièvrePierre Laurent-Puig
Dec 23, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E A EisenhauerJ Verweij
Feb 28, 2009·Nature Reviews. Drug Discovery·Andrew Beenken, Moosa Mohammadi
Jan 23, 2010·Nature Reviews. Cancer·Nicholas Turner, Richard Grose
Nov 5, 2010·Molecular Cancer Research : MCR·Ellen Margrethe HaugstenJørgen Wesche
Nov 17, 2012·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Rebecca S HeistA John Iafrate
Apr 27, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Friederike GökeSven Perner
May 10, 2013·Molecular Cancer Therapeutics·Kilian M GustPeter C Black
Oct 9, 2013·Anti-cancer Drugs·Yi HuJingxin Zhang
Nov 5, 2013·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Matthias PreusserPeter Birner
Nov 23, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·R DienstmannJ Tabernero
Apr 29, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Murry W WynesLynn E Heasley
May 24, 2014·British Journal of Cancer·N CihoricC Tapia
Mar 17, 2015·Wiley Interdisciplinary Reviews. Developmental Biology·David M Ornitz, Nobuyuki Itoh
May 28, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Friederike GökeSven Perner
Sep 17, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Teresa HelstenRazelle Kurzrock
Mar 5, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Koos KooleStefan M Willems
Jun 2, 2016·International Journal of Molecular Medicine·Masaru Katoh
Dec 20, 2016·Trends in Pharmacological Sciences·Masaru Katoh
Feb 17, 2018·ChemMedChem·Marie-Pierre CollinHolger Hess-Stumpp
Aug 4, 2018·Molecular Carcinogenesis·Xiangdong ZhaoYong Teng
Oct 28, 2018·Nature Reviews. Clinical Oncology·Masaru Katoh
Mar 1, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·R DienstmannJ Tabernero

❮ Previous
Next ❯

Citations

Jun 23, 2019·Cells·Takahiko Murayama, Noriko Gotoh
Sep 17, 2020·Expert Review of Clinical Pharmacology·Alberto D'AngeloGiandomenico Roviello
Oct 20, 2020·Expert Opinion on Investigational Drugs·Sreenivasa R ChandanaDaruka Mahadevan
Aug 14, 2020·The Oncologist·Rohan GarjeYousef Zakharia
Dec 1, 2020·Expert Review of Anticancer Therapy·Kamaneh Montazeri, Guru Sonpavde
Dec 6, 2019·Therapeutic Advances in Medical Oncology·Chiara CasadeiUgo De Giorgi
Oct 5, 2020·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Anissa MoktefiChristophe Tournigand
Dec 8, 2019·Expert Review of Clinical Pharmacology·Kamaneh Montazeri, Joaquim Bellmunt
Mar 18, 2021·Critical Reviews in Oncology/hematology·Daniel HerchenhornJuliana Tarouquella
Apr 21, 2021·ACS Applied Materials & Interfaces·Chengpan LiWeiping Ding
May 5, 2021·Investigative and Clinical Urology·Whi An Kwon, Ho Kyung Seo
Jul 26, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Alberto ServettoCarlos L Arteaga
Oct 22, 2020·Organic Letters·Rachel R KnappNeil K Garg
Oct 14, 2020·Current Drug Targets·Shilpi AgrawalThallapuranam Krishnaswamy Suresh Kumar
Oct 2, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mònica Sánchez-GuixéVioleta Serra
Jan 4, 2022·Endocrinology·Cecilia Pérez PiñeroClaudia Lanari

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsies
competition binding
xenograft

Clinical Trials Mentioned

NCT01976741
NCT03410693
NCT03473756
NCT02592785

Software Mentioned

PanLabs
R

Related Concepts

Related Feeds

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.