Tyrosine kinase inhibitors: application of chemical and discovery proteomics to the problem of chemotherapeutic toxicity in cancer patients

About this opportunity

Conventional chemotherapy for numerous cancers involves toxic and damaging drugs that cause severe side effects in patients. Scientists have for decades searched for the ‘magic bullet’ that would target only cancer cells, thereby reducing or eliminating the toxic effects of treatment. While this has yet to be fully achieved, huge strides have been made in the development of more specific drugs. One example of this is the group of tyrosine kinase inhibitors (TKIs).

Osimertinib is a TKI used to treat lung cancer in patients with mutations in their epidermal growth factor receptor (EGFR). The drug binds irreversibly to the receptor, thereby limiting EGF-stimulated proliferation. Despite the improved targeting of the drug compared to earlier therapies, many patients receiving TKIs develop severe liver and gastrointestinal (GI) toxicity, limiting the utility of the drug and impairing the quality of life for patients. Toxicity is believed to be a consequence of irreversible binding of the drug/metabolites to proteins other than the intended targets (off-target toxicity). This project will use cutting-edge technology to identify the off-target proteins, to decipher the consequences and potential mitigation of off-target binding, and to chemically engineer better drugs for the future.

The study will be carried out using human liver and GI organoids. These are mini organs-in-a-test-tube that mimic many of the functions of cells or tissues in the body. They are becoming increasingly vital to the study of disease and drug safety because they outperform conventional cell culture methods and they don’t require animal models. You will be trained on all aspects of organoid generation and maintenance.

Who is this opportunity for?

This project is open to self-funded UK and international applicants. A minimum 2.1 undergraduate (Bachelor’s) degree, or a relevant master’s degree, is required (or equivalent qualifications for international candidates).

Additional costs

We understand that budgeting for your time at university is important, and we want to make sure you understand any costs that are not covered by your tuition fee. This could include buying a laptop, books, or stationery.

Find out more about the additional study costs that may apply to this project.

Funding your PhD

This opportunity is for students with their own funding. Funding should cover course fees, living expenses and research expenses (bench fees). The research group cannot provide supplementary funding or provide advice about how to apply for funding.

If you're a UK national, or have settled status in the UK, you may be eligible to apply for a Postgraduate Doctoral Loan worth up to £30,301 to help with course fees and living costs.

There’s also a variety of alternative sources of funding. These include funded research opportunities and financial support from UK research councils, charities and trusts. Your supervisor may be able to help you secure funding.

Contact us

Have a question about this research opportunity or studying a PhD with us? Please get in touch with us, using the contact details below, and we’ll be happy to assist you.