PMID: 25749034Mar 10, 2015Paper

NPM/ALK mutants resistant to ASP3026 display variable sensitivity to alternative ALK inhibitors but succumb to the novel compound PF-06463922

Oncotarget
Luca MologniC Gambacorti-Passerini

Abstract

ALK is involved in the onset of several tumors. Crizotinib (XalkoriTM), a potent ALK inhibitor, represents the current front-line treatment for ALK+ NSCLC and shows great clinical efficacy. However, resistant disease often develops after initial response. ASP3026 is a novel second-generation ALK inhibitor with activity on crizotinib-resistant ALK-L1196M gatekeeper mutant. As resistance is likely to be a relevant hurdle for any drug, we sought to determine the resistance profile of ASP3026 in the context of NPM/ALK+ ALCL. We selected six ASP3026-resistant cell lines by culturing human ALCL cells in the presence of increasing concentrations of drug. The established resistant cell lines carry several point mutations in the ALK kinase domain (G1128S, C1156F, I1171N/T, F1174I, N1178H, E1210K and C1156F/D1203N were the most frequent) that are shown to confer resistance to ASP3026 in the Ba/F3 cell model. All mutants were profiled for cross-resistance against a panel of clinically relevant inhibitors including ceritinib, alectinib, crizotinib, AP26113 and PF-06463922. Finally, a genetically heterogeneous ASP3026-resistant cell line was exposed to second-line treatment simulations with all inhibitors. The population evolved according t...Continue Reading

References

Jul 4, 1997·The Journal of Biological Chemistry·W HemmerS S Taylor
Feb 8, 2003·The Lancet Oncology·Carlo B Gambacorti-PasseriniLeonardo Scapozza
Oct 13, 2006·Journal of Molecular Endocrinology·Luca MologniCarlo Gambacorti-Passerini
Oct 17, 2008·Nature·Isabelle Janoueix-LeroseyOlivier Delattre
Jul 17, 2010·The Biochemical Journal·Christian C LeeGlen Spraggon
Oct 29, 2010·The New England Journal of Medicine·Young Lim ChoiUNKNOWN ALK Lung Cancer Study Group
Sep 29, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Johannes M HeuckmannRoman K Thomas
Nov 1, 2011·Chemical Biology & Drug Design·Sen ZhangVictor M Rivera
Jan 12, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robert C DoebeleD Ross Camidge
Jan 20, 2012·Nature·Mel Greaves, Carlo C Maley
May 23, 2012·Expert Opinion on Investigational Drugs·Luca Mologni
Jun 5, 2012·Biochemical and Biophysical Research Communications·Hui-Yong Sun, Feng-Qin Ji
Dec 15, 2012·Molecular Cancer Research : MCR·Monica CecconCarlo Gambacorti-Passerini
Nov 10, 2013·Nature Medicine·Piro LitoDavid B Solit
Mar 29, 2014·The New England Journal of Medicine·Alice T ShawJeffrey A Engelman
Mar 29, 2014·Cancer Discovery·Luc FribouletJeffrey A Engelman
Apr 17, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Sai-Hong Ignatius OuVincent A Miller
Jul 31, 2014·The Journal of Pharmacology and Experimental Therapeutics·Shinji YamazakiPaolo Vicini
Sep 18, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ryohei KatayamaAlice T Shaw
Nov 14, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Sai-Hong Ignatius OuVincent A Miller

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Citations

Dec 15, 2015·Expert Review of Anticancer Therapy·Ittai B MullerGodefridus J Peters
Nov 1, 2017·Journal of Cheminformatics·Dilip NarayananRichard A Engh
Jan 5, 2017·Cold Spring Harbor Molecular Case Studies·Vijaykumar R HollaGeorge R Simon
Oct 16, 2016·International Journal of Clinical Oncology·Helen Ma, Maher Abdul-Hay
Jun 7, 2017·The New England Journal of Medicine·Solange PetersUNKNOWN ALEX Trial Investigators
Dec 22, 2015·Biomarkers in Cancer·Amit Dipak AminJonathan H Schatz
Jul 26, 2019·Journal of Hematology & Oncology·Bhawana GeorgeHesham M Amin

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