Identifying Therapies to Combat Epithelial Mesenchymal Plasticity-Associated Chemoresistance to Conventional Breast Cancer Therapies Using An shRNA Library Screen
Sugandha Bhatia, Tony Blick, Cletus Pinto, Mark Waltham, James Monkman, Ekaterina Ivanova, Pamela M Pollock, Shivashankar H Nagaraj, Adrian P Wiegmans, Izhak Haviv, Kaylene J Simpson, Erik W Thompson
CANCERS | MDPI | Published : 2020
BACKGROUND: Breast cancer (BC) is a heterogeneous disease for which the commonly used chemotherapeutic agents primarily include the anthracyclines (doxorubicin, epirubicin), microtubule inhibitors (paclitaxel, docetaxel, eribulin), and alkylating agents (cyclophosphamide). While these drugs can be highly effective, metastatic tumours are frequently refractory to treatment or become resistant upon tumour relapse. METHODS: We undertook a cell polarity/epithelial mesenchymal plasticity (EMP)-enriched short hairpin RNA (shRNA) screen in MDA-MB-468 breast cancer cells to identify factors underpinning heterogeneous responses to three chemotherapeutic agents used clinically in breast cancer: Doxoru..View full abstract
Awarded by US-DOD IDEA grant
Awarded by National Breast Cancer Foundation National Collaborative Research Program grant
This work E.W.T. and I.H. were supported in part by US-DOD IDEA grant BC 084667 and a National Breast Cancer Foundation National Collaborative Research Program grant (CG-10-04) to E.W.T. The Translational Research Institute (TRI) receives support from the Australian Government. We would like to thank the core facility teams based at TRI for their technical assistance and Aleksandra Rajapakse for the validation of an experimental assay. The Victorian Centre for Functional Genomics (K.J.S.) is funded by the Australian Cancer Research Foundation (ACRF), the Australian Phenomics Network (APN) through funding from the Australian Government's National Collaborative Research Infrastructure Strategy (NCRIS) program, the Peter MacCallum Cancer Centre Foundation and the University of Melbourne Research Collaborative Infrastructure Program. During the course of the study, S.B. was supported by a QUTPRA scholarship.