Abstract B34: PIM kinase as a novel therapeutic target for triple-negative breast cancer

The greatest clinical challenge in treating breast cancer occurs in those patients whose tumors lack expression of the estrogen and progesterone receptors and that of the HER2 oncoprotein. No targeted therapeutic strategies currently exist against this aggressive type of "triple negative" breast cancer (TNBC) due to lack of validated targets. We previously found that MYC mRNA, protein, and its signaling were disproportionally elevated in TN compared to receptor positive (RP) breast cancer. We sought to take advantage of the unique molecular feature found in this tumor type to identify potent and effective treatment strategies. Since MYC is an oncogenic transcription factor, rationally designed small molecule inhibitors that can directly inhibit its activity are not available for clinical use. An alternative approach to selectively kill MYC-driven tumors is to inhibit those proteins that are indispensable for the viability of such tumors, but are not essential in non-tumorigenic cells. This form of "indirect" treatment strategy has become known as the "synthetic-lethal" approach. To identify novel targets that are readily druggable for treating MYC-driven TNBC, we conducted a kinome MYC synthetic lethal shRNA screen in non-immortalized human mammary epithelial cells expressing a 4-hydroxytamoxifen (TAM)-activatable MycER transgene (HMEC-MycER). Of 600 human kinases targeted by 2,000 individual shRNA clones, 9 kinases were identified as hits as they were essential specifically ...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Targeted Therapies: Poster Presentations - Proffered Abstracts Source Type: research