Gary Middleton

Professor Gary Middleton is a Medical Oncologist who specialises in lung cancer and colorectal cancer. He has many years of experience in patient treatment, and also in development of novel clinical trials.  Appointed to a chair of Medical Oncology at Birmingham in 2013, he has built up a strong clinical and translational research programme. . Gary is Chair of the Experimental Cancer Medicine Centre Network, Director of the Birmingham ECMC and Lead for the Birmingham CRUK Clinical Academic Training Programme. A key interest is in stratified approaches to patient treatment, and Gary has a strong presence in UK stratified medicine clinical trials. He is Chief Investigator for the National Lung Matrix Trial, a multi-centre, multi-arm, molecularly stratified clinical trial programme for UK patients with lung cancer (Nature, 2020). 

He is Translational Lead for the DETERMINE trial which seeks to understand the impact of the genomic, transcriptional and immunological context on which the targeted mutation is inscribed on outcome with genotype-matched targeted therapy (Ann Oncol, 2023). A fundamental part of this work is to uncover the mutational, epigenomic and inflammatory processes that promote the development of oncogene addicted cancers. He is also interested in stratification approaches for immunotherapy and leads on the ANICCA trial, a phase II study in high class II expressing microsatellite stable colorectal cancer, a study directly translating the clinic work from his laboratory programme exploring the determinants and dynamics of class II expression in cancer (Cancer Res Comms, 2023).

One particular area of active study is myeloid derived suppressor cells and tumour associated macrophages, which suppress tumour-specific immune responses particularly in liver metastases and the lab has developed a suite of human models to understand how best to target these to improved ICB outcomes in patients with liver metastases. The discovery of novel predictors of checkpoint blockade toxicity is a particularly key area of current research and the group have recently published data showing a pre-treatment lack of Bregs in patients developing severe immune related adverse events (irAEs) in lung cancer patients (Nat Comms, 2022). We are currently exploring the underlying failure of this induction and have developed clinical grade assays to interrogate Breg status as clinically useable predictive biomarker for the development of severe irAEs.