Identifying new indications and novel combinations for the tyrosine kinase inhibitor neratinib in non-breast, HER-driven cancers

A PhD studentship is available to a highly motivated candidate who wishes to pursue research in identifying new indications and novel combinations for the tyrosine kinase inhibitor (TKI) neratinib in non-breast, HER-driven cancers.

This project is funded through an SFI Strategic Partnership Programme and will be based at the National Institute for Cellular Biotechnology (NICB), DCU.

Project Description

The HER-family, particularly EGFR and HER2, are oncogenic drivers in multiple cancer types including lung, breast, colorectal, glioblastoma and pancreatic cancers. Neratinib is approved for the treatment of HER2+ breast cancer but as a pan-HER-family tyrosine kinase inhibitor (TKI), neratinib may have potential as a therapy in other HER-family driven cancer types. The aim of this project is to identify novel cancer types with potential for treatment with neratinib, or neratinib in combination with other HER2-targeted therapies and disease-relevant chemotherapies. The candidate will utilise cell line models to screen for synergistic combinations and understand the underlying mechanisms of action. The most promising combinations will be tested in vivo. Gastric and oesophageal cancers will be a particular focus. Reported HER2+ frequencies range from 6 – 29.5 % in gastric cancer and 15- 29% in oesophageal adenocarcinomas. There are currently no HER2-targeted TKIs approved for these cancers. The study of innate and acquired resistance of gastric/oesophageal cancers to targeted therapies has been hampered by the lack of model systems capable of reflecting the original tumour and modelling drug screening and molecular phenotype. As part of the project, 3D organoid models of gastric and oesophageal cancer will be developed from patient tumours to better re-capitulate the clinical setting.

This ultimate aim of this project is to provide pre-clinical rationale for clinical trials of neratinib and/or neratinib combinations outside HER2+ breast cancer.

Candidates will be supervised by Prof John Crown (Saint Vincent’s University Hospital/DCU) and Dr Denis Collins (DCU). The project will be based in the Collins research group, Cancer Biotherapeutics, at the NICB, DCU that has local, national and international research and clinical collaborators.

For more information about this project, please contact Dr Denis Collins: [Email Address Removed]

We are seeking highly motivated candidates with a minimum 2.1H (or equivalent), BSc or MSc in Biochemistry, Cell Biology, Molecular Biology or related fields.

Closing Date for Applications: 12th August 2020
Starting Date for PhD: 1st October 2020

To apply, candidates should submit a detailed CV, a personal statement that outlines research interests, past experience and motivation to complete a PhD (2 pages maximum), and contact information for two academic referees by email to: [Email Address Removed]

Unfortunately, we are unable to provide individual feedback to applicants.
Shortlisted candidates will be invited for interview (online).

For more information on the NICB and the Cancer Biotherapeutics group see: https://nicb.ie/portfolio-view/cancer-biotherapeutics/