Molecular Oncology Group

One of the group's aims is targeting aberrant Fibroblast Growth Factor Receptors (FGFRs) in cancer. Activation of the FGFRs is one of the most common oncogenic events in cancer, which is frequently associated with a poor outcome. We are interested in identifying determinants of sensitivity to FGFR inhibitors and mechanisms of resistance.

The group also has a focus on targeting the dependence on specific cell cycle kinases in breast cancer, in particular WEE1 inhibitor combinations and the targeting of CDK4/6 in breast cancer.

The group is also interested in non-invasive analysis of breast tumour phenotypes through analysis of circulating free DNA, and the potential to use such assays to personalise breast cancer therapy and dissect intra-tumoural heterogeneity.

Professor Turner is Chief Investigator of a number of clinical trials of targeted therapy in breast cancer, with these trials focused on the delivery of personalised therapy for breast cancer.

Targeting aberrant fibroblast growth factor receptor signalling in cancer

Activation of fibroblast growth factor receptors (FGFR) is one of the most common oncogenic events in cancer, and we are interested in particular in cancers with FGFR amplification. We seek to understand how amplification of the receptor is oncogenic, what predicts whether a cancer responds to FGFR inhibition, what are the mechanisms of resistance, and how this can inform the development of rational combination strategies.

Targeting dependence on cell cycle kinases in breast cancer

Control of the cell cycle is frequently aberrant in cancer, and this presents a potential therapeutic strategy, as cancers become reliant on specific kinases to either promote cell cycle progression or restrain inappropriate cell cycle progression in the presence of DNA damage. Particular areas of research include the potential to target CDK4/6 in luminal breast cancer, and WEE1-chemotherapy combination in TP53 mutant and triple negative breast cancer.

Non-invasive analysis of breast cancer tumour genetics

Breast cancer treatment increasingly relies on the identification of particular somatic mutations to direct appropriate targeted therapy. Cancer DNA can be detected in the blood of patients with breast cancer, and this potentially presents a non-invasive way of assessing breast cancer genetics. We have developed assays of HER2 in such circulating free DNA that show a high concordance with tumour derived HER2 status, and are developing and validating high sensitivity digital PCR assays for other breast cancer oncogenes. We are also investigating the use of next generation sequencing of circulating free DNA, and whether this presents a tool to dissect intra-tumoural genetic heterogeneity in advanced breast cancer.

Delivery of personalised therapy for breast cancer

Dr Nicholas Turner is chief investigator of a number of targeted therapies in breast cancer, with the aim of assessing the potential to target specific genetic mutations and amplifications in cancer including FGFR1 amplification and PIK3CA mutation.