Assessing the Potential Value of Repurposing Tricyclic Antidepressants (TCAs) for Treating Breast-to-brain Metastases
Self-funded PhD students only
School of Pharmacy and Biomedical Sciences
February and October
Open all year round
This is a self-funded, 3 year full-time or 6 year part-time PhD studentship, to commence in October 2019 or February 2020. The project is supervised by Dr Qian An.
Breast cancer, along with lung cancer and melanoma, is one of the most aggressive human cancers in terms of developing brain metastasis, a condition which typically has a very poor prognosis. The negativity of the prognosis is mainly due to the presence of the blood–brain barrier (B-BB) that prevents a large number of antineoplastic agents from entering the brain.
However, previously published data has shown that tricyclic antidepressants (TCAs) can induce apoptosis (cell death) by targeting mitochondria in glioma, metastatic melanoma, lung and colorectal cancer cells. To date, the anti-cancer activity of TCAs in breast cancer cells has not been reported.
The aim of this PhD project is to investigate the activities of TCAs in breast cancer cells and evaluate potential drug repurposing for the treatment of breast-to-brain metastases.
The work will include:
- Analysis of cell viability, cytotoxicity and apoptosis activation using the ApoTox-Glo Triplex Assay
- Exposure of a number of breast cancer cell lines and normal breast epithelial primary cultures to amitriptyline, nortriptyline and norclomipramine (a metabolic product of clomipramine in the brain) followed
- Drug activity in each cell line will be assessed by the inhibitory concentration 50 (IC50) value
- establishing the possible impact of TCAs on mitochondria, through the analysis of activity in individual mitochondrial respiratory chain complexes, mitochondrial Reactive Oxygen Species (ROS) levels and membrane potential
- The investigation of of mitochondrial DNA (mtDNA) variations as potential biomarkers to assess drug sensitivity
Self-funded PhD students only. PhD full-time and part-time courses are eligible for the Government Doctoral Loan.
Home/EU/CI full-time students: £4,260 p/a*
Home/EU/CI part-time students: £2,130 p/a*
International full-time students: £15,100 p/a*
International part-time students: £7,550 p/a*
By Publication Fees 2018/2019
Members of staff: £1,550 p/a*
External candidates: £4,260 p/a*
*All fees are subject to annual increase.
Bench fees (in GBP)
Year 1: £10000
Year 2: £11000
Year 3: £9500
- A good honours degree or equivalent in a relevant subject or a master’s degree in an appropriate subject.
- Exceptionally, equivalent professional experience and/or qualifications will be considered. All applicants are subject to interview.
- English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.
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Interview date: TBC