Targeting ITGA2–FAK–mTOR Signalling to Overcome FGFR Inhibitor Resistance in Cancer (PhD Studentship) Kingston University in United Kingdom

Project Overview: This PhD studentship at Kingston University focuses on overcoming resistance to FGFR inhibitors in cancer, specifically targeting the ITGA2–FAK–mTOR signalling axis. The project is situated within the Faculty of Health, Science, Social Care and Education and leverages robust in-house models of drug resistance in both breast and cervical cancer.

Background: Fibroblast Growth Factor (FGF) signalling is crucial for cellular processes such as proliferation, migration, and survival. In breast and cervical cancers, aberrant FGFR activation supports tumour progression and metastasis. Although FGFR inhibitors show clinical promise, resistance develops rapidly through mechanisms like pathway rewiring, cell-state plasticity, and changes in the tumour microenvironment. Understanding these adaptive processes is essential for developing next-generation therapies.

Current Research: The lab has established cell line models resistant to FGFR inhibitors (e.g., AZD4547) in breast cancer, validated through functional assays and pathway analysis. In cervical cancer, three resistant lines (CaSki, HeLa, SiHa) have been developed, showing transcriptomic and phenotypic shifts, including activation of ITGA2–FAK signalling and persistent mTOR activity. These models provide a platform to study convergent and divergent resistance mechanisms and identify biomarkers of therapeutic response.

PhD Project Aims: The project will integrate transcriptomic and proteomic data from resistant cancer lines to identify shared pathways (such as ITGA2–FAK signalling, mTOR activation, and EMT-associated changes) that drive therapeutic escape. The student will validate these molecular signatures using targeted inhibitors and develop rational combination therapies by testing FGFR inhibitors alongside agents targeting FAK, mTORC1/2, MAPK, or integrin signalling. Additional work will explore the role of the tumour microenvironment using 3D organotypic cultures and co-culture models.

Mechanistic and Translational Validation: The project will employ loss- and gain-of-function approaches (siRNA/CRISPR, overexpression, pharmacological inhibitors) to dissect the role of ITGA2–FAK in maintaining resistance and invasive phenotypes. Advanced imaging and molecular techniques will clarify how ITGA2 relocalisation and focal adhesion dynamics contribute to metastatic behaviour. Translational studies will combine FGFR inhibitors with FAK or integrin-targeting agents in vitro and in organoid models, and assess ITGA2/FAK as biomarkers in patient samples.

Eligibility: Applicants should have a strong background in biological or biomedical sciences, with experience in molecular or cell biology and a keen interest in cancer research. English language proficiency is required for non-native speakers.

Funding: The project is part of the Graduate School studentships competition for October 2026 entry. Applicants should apply as 'self-funded'; successful candidates will have their funding status updated internally. See the Kingston University PhD Studentships page for details.

Application Deadline: 4 March 2026

How to Apply: Submit your application via the Kingston University Research Degrees portal, selecting 'self-funded' as the funding option. Further details are available on the university website.