BPR1J373, a novel multitargeted kinase inhibitor, effectively suppresses the growth of gastrointestinal stromal tumor

Cancer Science
Hui-Jen TsaiLi-Tzong Chen

Abstract

Gastrointestinal stromal tumor (GIST) is a type of KIT-driven cancer. KIT gene mutations are found in approximately 80% of GISTs, and most of these mutations occur in exon 9 and exon 11. Imatinib has been successfully used as a first-line treatment for advanced GIST, with a significant improvement in progression-free survival (PFS) and overall survival. However, disease progression might develop due to primary or secondary resistance to imatinib. Sunitinib and regorafenib have been approved as second- and third-line treatments for advanced GIST patients, with median PFS values of 6.8 and 4.8 months, respectively. However, these relatively modest improvements in PFS underscore the need for more effective KIT inhibitors. BPR1J373 is a multitargeted kinase inhibitor that has been shown to inhibit the proliferation of KIT-driven acute myeloid leukemia cells in vitro and in vivo. In this study, we found that BPR1J373 inhibited proliferation and induced apoptosis by targeting KIT in GIST cells with KIT gene mutations. BPR1J373 also induced cell cycle arrest and senescent change in KIT-mutant GIST48 cells, probably by targeting aurora kinase A. In the KIT-null COS-1 cell-based system, BPR1J373 effectively inhibited KIT with single or ...Continue Reading

References

Apr 5, 2001·The New England Journal of Medicine·B J DrukerC L Sawyers
Mar 1, 2002·The New England Journal of Medicine·Hagop KantarjianUNKNOWN International STI571 CML Study Group
Aug 16, 2002·The New England Journal of Medicine·George D DemetriHeikki Joensuu
Dec 4, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael C HeinrichJonathan A Fletcher
Dec 24, 2003·The Cancer Journal·Diane D Davey
Jun 3, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Cristina R AntonescuRonald P DeMatteo
Dec 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·O M GrbovicN Rosen
Mar 23, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eva WardelmannPeter Hohenberger
Apr 21, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Maria Debiec-RychterUNKNOWN Australasian GastroIntestinal Trials Group
Feb 1, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Charles D BlankeHeikki Joensuu
Jul 16, 2008·The Journal of Pathology·B LieglJ A Fletcher
Oct 29, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael C HeinrichGeorge D Demetri
Feb 4, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·UNKNOWN Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST)
Dec 1, 2010·Cancer Chemotherapy and Pharmacology·Mrinal M Gounder, Robert G Maki
Feb 18, 2011·Diagnostic Molecular Pathology : the American Journal of Surgical Pathology, Part B·Zoltán SápiGyörgy Bodoky
Nov 18, 2011·Nature Reviews. Cancer·Christopher L CorlessMichael C Heinrich
Jun 6, 2012·Molecular Cancer Therapeutics·Michael C HeinrichJonathan A Fletcher
Apr 30, 2013·Lancet·Heikki JoensuuChristopher L Corless

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft

Software Mentioned

WinMDI

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.