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Brk and mTOR signalling: implications for Taxol resistance


   Biosciences

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  Dr A Harvey  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

One of the major causes of death amongst breast cancer patients is due to the development of distal metastases and the acquisition of resistance to chemotherapeutic agents. There is a scientific and clinical need to understand the alterations in cellular signalling pathways that could contribute to chemotherapeutic resistance in breast cancer.

Our preliminary data implicate both that Brk expression and mTOR signalling are up-regulated in resistance to Taxol, a chemotherapeutic drug that is widely used in treating breast cancer. This project seeks to investigate the involvement of Brk, a kinase overexpressed in up to 86% of breast cancers, in regulating mTOR signalling in the development of Taxol resistance. You will examine the gene expression of mTOR components by real-time Q-PCR in Brk-suppressed and Brk-overexpressing breast cancer cells. Relative phosphorylation levels will also be determined using phospho-specific antibody arrays. To determine whether mTOR, is a Brk substrate, we will immunoprecipitate Brk and western blot for members of the mTOR pathway. We will also examine whether Brk influences the effects of mTOR inhibitors and whether combinations of Brk and mTOR inhibitors alter sensitivity to Taxol in Taxol-resistant cells


Funding Notes

Brunel offers a number of funding options to research students that help cover the cost of their tuition fees, contribute to living expenses or both. See more information here: https://www.brunel.ac.uk/research/Research-degrees/Research-degree-funding. The UK Government is also offering Doctoral Student Loans for eligible students, and there is some funding available through the Research Councils. Many of our international students benefit from funding provided by their governments or employers. Brunel alumni enjoy tuition fee discounts of 15%.

References

Hare, SH. and Harvey, AJ. (2017) 'mTOR Function and Therapeutic Targeting in Breast Cancer'. American Journal of Cancer Research, 7 (3). pp. 383 - 404.
Hussain, HA. and Harvey, A. (2014) 'Evolution of breast cancer therapeutics: Breast tumour kinase’s role in breast cancer and hope for breast tumour kinase targeted therapy'. World Journal of Clinical Oncology, 5 (3). pp. 299 - 310. ISSN: 2218-4333

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