Assessing the Potential Value of Repurposing Tricyclic Antidepressants (TCAs) for Treating Breast-to-brain Metastases
PhDs and postgraduate research
Self-funded PhD students only
School of Pharmacy and Biomedical Sciences
Open all year round
This is a self-funded, 3 year full-time or 6 year part-time PhD studentship. 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
Fees and funding
Self-funded PhD students only. PhD full-time and part-time courses are eligible for the Government Doctoral Loan.
Bench fees (in GBP)
Year 1: £10000
Year 2: £11000
Year 3: £9500
2020/2021 entry (for October 2020 and February 2021 entries)
Home/EU/CI full-time students: £4,407 p/a
Home/EU/CI part-time students: £2,204 p/a
International full-time students: £16,400 p/a
International part-time students: £8,200 p/a
PhD by Publication
External candidates £4,407 p/a
Members of staff £1,680 p/a*
2021/2022 entry (for October 2021 and February 2022 entries)
PhD and MPhil
Home/EU/CI full-time students: £4,407 p/a*
Home/EU/CI part-time students: £2,204 p/a*
International full-time students: £17,600 p/a
International part-time students: £8,800 p/a
All fees are subject to annual increase.
PhD by Publication
External Candidates £4,407 p/a*
Members of Staff £1,720 p/a*
If you are an EU student starting a programme in 2021/22 please visit this page.
*This is the 2020/21 UK Research and Innovation (UKRI) maximum studentship fee; this fee will increase to the 2021/22 UKRI maximum studentship fee when UKRI announces this rate in Spring 2021.
Some PhD projects may include additional fees – known as bench fees – for equipment and other consumables, and these will be added to your standard tuition fee. Speak to the supervisory team during your interview about any additional fees you may have to pay. Please note, bench fees are not eligible for discounts and are non-refundable.
- 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