TNK2 Tyrosine Kinase as a Novel Therapeutic Target in Triple-Negative Breast Cancer
Abstract
Triple-negative breast cancers (TNBCs) represent only 10 percent-15 percent of all breast cancers; however, they are highly aggressive and have a higher rate of metastasis and a poorer prognosis than other breast cancer subtypes. The primary reason contributing to the poor clinical outcomes associated with TNBCs is the lack of clearly defined therapeutic targets. We observed a novel non-receptor tyrosine kinase,TNK2 (also known as ACK1), to be hyperphosphorylated and activated in highly aggressive TNBC cells. Suppression of TNK2 by specific siRNAs significantly reduced the proliferation, colony formation, and invasive ability of TNBC cells. Our proposed study will allow us to validate TNK2 as novel therapeutic target for TNBC patients. Novel breast cancer therapies directed against TNK2 can be developed based on our discoveries, which can decrease the recurrence and metastatic disease of TNBCs and eventually reduce breast cancer death. The objective of this proposal is to evaluate the therapeutic potential of TNK2 in the treatment of TNBCs. In parallel, pharmacological inhibitor,DZ1-067 will be evaluated as a therapeutic target in vitro and in preclinical animal models. To elucidate the signaling network of TNK2 in oncogenesis of TNBCs, we will perform a LC-MS/MS-based comprehensive phosphoproteomic study to identify signaling cascades modulated by TNK2. This study will define TNK2 as a novel therapeutic target for TNBCs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2018
- Accession Number
- AD1091522
Entities
People
- Nupam P. Mahajan
Organizations
- H. Lee Moffitt Cancer Center & Research Institute