Targeting the Breast Cancer Microenvironment with Repositioned Combination Antihypertensives to Inhibit Key Oncogenic Signalling Pathways Kingston University in United Kingdom

This PhD project at Kingston University focuses on the innovative strategy of drug repositioning to target the breast cancer microenvironment using combination antihypertensive therapies. Despite significant advances in cancer research, the development of new anticancer drugs is often hampered by long timelines, high costs, and regulatory challenges. Drug repositioning—repurposing approved therapeutics for new cancer applications—offers a promising route to accelerate treatment availability and reduce development risks.

Breast cancer remains the most prevalent cancer worldwide, accounting for over 2.3 million new cases annually and more than 30% of all cancers diagnosed in women. Current treatments, including surgery and chemotherapeutic regimens, are limited by tumour heterogeneity, therapy resistance, and the complexity of the tumour microenvironment (TME). Recent studies suggest that antihypertensive drugs, spanning various subclasses, may modulate tumour biology, influence stromal interactions, and alter key signalling pathways within the breast cancer microenvironment. Some antihypertensives have shown promising anticancer or anti-metastatic effects, though findings are mixed.

This project will systematically evaluate the therapeutic potential of selected antihypertensive drugs—such as diuretics, ACE inhibitors, β-blockers, and angiotensin receptor blockers—both as monotherapies and in combination with small molecule inhibitors like verteporfin. Verteporfin, known for its role in photodynamic therapy, directly inhibits the YAP/TAZ-TEAD transcriptional pathway, a key driver of proliferation, stemness, angiogenesis, and therapy resistance in breast cancer. The combination of RAS inhibition and verteporfin-mediated YAP/TAZ blockade represents a rational, synergistic approach to suppress tumour progression and resistance.

The project’s three main aims are: (1) to assess the anticancer activity of antihypertensive drugs across established breast cancer cell lines, evaluating effects on proliferation, viability, migration, invasion, and microenvironment-related phenotypes in both 2D and 3D cultures, as well as in vivo models; (2) to investigate the mechanistic effects on major breast cancer signalling pathways, with a focus on understudied pathways such as AXL/TAM and RhoA/ROCK; and (3) to characterise microenvironment-specific responses, particularly how drug combinations influence stromal/tumour interactions, stress responses, and signalling crosstalk contributing to tumour progression and resistance.

Students will receive comprehensive training in cell and molecular biology, biochemistry, and analytical techniques, including immunoblotting, immunofluorescence, confocal microscopy, PCR, scratch-based assays, mass spectrometry, RNA-sequencing analysis, and the generation of 3D culture models and in vivo analysis. The project is part of a collaborative effort between Kingston University and other institutes, providing a rich research environment.

Applicants should hold a first or upper second-class honours degree in a relevant biological or biomedical discipline. The project is included in the Graduate School studentships competition for October 2026 entry. Applicants should apply as 'self-funded'; this status will be updated if a studentship is awarded. The application deadline is March 4, 2026.