Abstract LB-067: Identifying novel and druggable targets in a triple negative breast cancer cell line using the Invitrogen LentiArray Human Kinase CRISPR Library

Autor: Chetana M. Revankar, Tufan Gökirmak, David R. Piper, Jason Sharp
Rok vydání: 2018
Předmět:
Zdroj: Cancer Research. 78:LB-067
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2018-lb-067
Popis: Breast cancer is the most commonly diagnosed cancer among women in worldwide and the second leading cause of death by cancer after lung cancer. Breast cancer can be broadly grouped into three main groups: HR+ (estrogen receptor positive and/or progesterone receptor positive), HER2+ (human epidermal growth factor receptor 2 positive) and triple-negative (HR- and HER2-). Hormone and anti-HER2 targeted therapies are available for receptor positive breast cancer types. However, because triple-negative breast cancer (TNBC) does not have estrogen, progesterone or HER2 receptors, there are no such targeted therapies available for this type of cancer. Currently, oncologists are resort to treating TNBC patients with traditional chemotherapy drugs, surgery and radiation. Thus, due to its poorer prognosis and fewer treatment options in comparison to other type of breast cancers, search for specific molecular targets and developing novel treatments for TNBC is one of the highest priorities of current breast cancer research. Protein kinases are involved in cell signaling cascades leading to cell proliferation, migration and survival in all cell types, and their dysregulation often leads to cancer. Due to their oncogenic roles, protein kinases have become a main focus of the targeted drug discovery efforts. Therefore development of novel high-throughput screening platforms that enable the identification of protein kinases or for that matter any gene, essential for tumor proliferation and viability is expected to advance oncogenic drug discovery efforts. In this study, we developed a loss-of-function screen for identifying essential kinases in a TNBC cell line, MDA-MB-231, using the Invitrogen™ LentiArray™ Human Kinase CRISPR Library. This arrayed lenti virus library targets 840 kinases with up to 4 different gRNAs per protein kinase for complete gene knockout. Our initial pilot screen identified polo-like kinase 1 (PLK1), checkpoint kinase 1 (CHK1) and cyclin-depended kinase 9 (CDK9) as essential kinases in MDA-MB-231 cell line and our current efforts focus on expanding this loss-of-function screen to the full kinase library and validation of the hits. Target identification and validation remains a significant challenge to translate to clinical trial outcomes and these generalized, functional genomic approaches may provide the next-generation platform to effectively bridge these gaps. Citation Format: Tufan Gokirmak, Jason Sharp, Chetana Revankar, David R. Piper. Identifying novel and druggable targets in a triple negative breast cancer cell line using the Invitrogen LentiArray Human Kinase CRISPR Library [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-067.
Databáze: OpenAIRE
Externí odkaz: