Abstract
Abstract B49: Epithelial-mesenchymal plasticity primes inherent resistance to targeted therapies
Cancer research (Chicago, Ill.), Vol.76(7_Supplement), pp.B49-B49
04/01/2016
DOI: 10.1158/1538-7445.TUMMET15-B49
Abstract
Abstract
The metastasis and acquisition of drug resistance in breast cancer cells has been linked to epithelial-mesenchymal transition (EMT). Directed therapies using kinase inhibitors and antibodies to target human epidermal growth factor receptor 2 (Her2) have served as a testament to the potential of molecular-targeted therapies in this breast cancer subtype. However, Her2-targeted therapies are plagued by the pitfalls of intrinsic and acquired resistance, particularly in the metastatic setting. To address these questions we conducted long-term treatments of Her2-transformed cells with TGF-β. This treatment regime resulted in a robust and plastic EMT phenotype as characterized by their CD44/CD24 profile. Following removal of stimuli, cells that had undergone TGF-β-induced EMT enter into a highly heterogeneous state, the importance of which is evidenced by their increased in vivo tumor growth metastatic capability. Importantly, the Lapatinib resistant cell population that arises following TGF-β-induced EMT can be readily eliminated via treatment with recently developed covalent inhibitors of fibroblast growth receptor (FGFR). Overall our data demonstrate that the EMT processes induced by physiologic cytokine stimulation are not only critical drivers of metastatic progression but they also are key events in producing secondary tumors that are poised to be inherently resistant to clinically used targeted molecular therapies.
Citation Format: Wells S. Brown, Michael Wendt. Epithelial-mesenchymal plasticity primes inherent resistance to targeted therapies. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B49.
Details
- Title: Subtitle
- Abstract B49: Epithelial-mesenchymal plasticity primes inherent resistance to targeted therapies
- Creators
- Wells S. BrownMichael Wendt
- Resource Type
- Abstract
- Publication Details
- Cancer research (Chicago, Ill.), Vol.76(7_Supplement), pp.B49-B49
- DOI
- 10.1158/1538-7445.TUMMET15-B49
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 04/01/2016
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984479560002771
Metrics
2 Record Views