View : 892 Download: 0
A novel combination treatment targeting BCL-XL and MCL1 for KRAS/BRAF-mutated and BCL2L1-amplified colorectal cancers
- Title
- A novel combination treatment targeting BCL-XL and MCL1 for KRAS/BRAF-mutated and BCL2L1-amplified colorectal cancers
- Authors
- Cho S.-Y.; Han J.Y.; Na D.; Kang W.; Lee A.; Kim J.; Lee J.; Min S.; Kang J.; Chae J.; Kim J.-I.; Park H.; Lee W.-S.; Lee C.
- Ewha Authors
- 조성엽; 나득채
- SCOPUS Author ID
- 조성엽; 나득채
- Issue Date
- 2017
- Journal Title
- Molecular Cancer Therapeutics
- ISSN
- 1535-7163
- Citation
- Molecular Cancer Therapeutics vol. 16, no. 10, pp. 2178 - 2190
- Publisher
- American Association for Cancer Research Inc.
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Colorectal cancer is the third most commonly diagnosed cancer in the world, and exhibits heterogeneous characteristics in terms of genomic alterations, expression signature, and drug responsiveness. Although there have been considerable efforts to classify this disease based on high-throughput sequencing techniques, targeted treatments for specific subgroups have been limited. KRAS and BRAF mutations are prevalent genetic alterations in colorectal cancers, and patients with mutations in either of these genes have a worse prognosis and are resistant to anti-EGFR treatments. In this study, we have found that a subgroup of colorectal cancers, defined by having either KRAS or BRAF (KRAS/BRAF) mutations and BCL2L1 (encoding BCL-XL) amplification, can be effectively targeted by simultaneous inhibition of BCL-XL (with ABT-263) and MCL1 (with YM-155). This combination treatment of ABT-263 and YM-155 was shown to have a synergistic effect in vitro as well as in in vivo patient-derived xenograft models. Our data suggest that combined inhibition of BCL-XL and MCL1 provides a promising treatment strategy for this genomically defined colorectal cancer subgroup. ©2017 AACR.
- DOI
- 10.1158/1535-7163.MCT-16-0735
- Appears in Collections:
- 의료원 > 의료원 > Journal papers
- Files in This Item:
There are no files associated with this item.
- Export
- RIS (EndNote)
- XLS (Excel)
- XML