Professor Gary Middleton

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Professor Gary Middleton is a consultant medical oncologist focussed on lung and colorectal cancer, with a research interest in understanding and therapeutically targeting the tumour microenvironment.
Position:

Professor of Medical Oncology, Institute of Immunology and Immunotherapy, University of Birmingham. 

Email: g.middleton@bham.ac.uk

 

Background and Research focus

Gary is a Medical Oncologist who specialises in lung cancer and colorectal cancer. He has 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 is building up a strong clinical research programme in lung and colorectal cancer. Gary also serves as a Clinical Director for the CRUK Birmingham Centre.

A key interest is in stratified approaches to patient treatment, and Gary has a strong presence in UK stratified medicine clinical trials. He is overall Chief Investigator for Matrix, a multi-centre, multi-arm, molecularly stratified clinical trial programme for UK patients with lung cancer. Gary is also a member of the trials management group and Chief Investigator for the BRAF arm of FOCUS4, a molecularly stratified multi-site, multi-arm, multi-stage randomised trials programme for UK patients with colorectal cancer. Synergising with this clinical focus on stratified treatment approaches, he is particularly interested in how the genetic/molecular phenotype of patients’ tumours correlates with the immunobiology of the tumour microenvironment.

Scientifically, Gary is focussed on understanding the tumour microenvironment and how this impacts on new therapeutic approaches, including novel immunotherapy strategies. One particular area of study is myeloid derived suppressor cells (MDSC), which are thought to suppress tumour-specific immune responses. He was recently awarded MRC Efficacy and Mechanism Evaluation funding to investigate the impact of the addition of Ruxolitinib, a STAT3 inhibitor, in mesothelioma. STAT3 inhibition targets MDSC populations in mesothelioma, and this is an area of active laboratory research, in which he collaborates with Dr Carmen De Santo and Dr Frank Mussai. He also collaborates with Professor Ben Willcox on tumour microenvironment-focussed work. In addition, he is co-lead for the immunobiology arm of TRACERx (Tracking Cancer Evolution through Therapy), a £14 million CRUK-funded study aiming to define how lung cancer develops spatially and temporally.

 

Expertise

lung cancer ; colorectal cancer ; pancreatic cancer; clinical trials; tumour microenvironment; myeloid derived suppressor cells; cancer vaccines; checkpoint blockade; personalised medicine; Matrix trial; TracerX; Focus4.

 

Other activities

Gary currently serves as a chief investigator for the PePS2, RUXSAC, TELOVAC, VIP trials and co-chief investigator for the TORCMEK trial. In addition to leading his own clinical research group, Gary is a member of the NCRI Lung Cancer Clinical Studies Group, the advanced lung cancer sub-group, the advanced colorectal sub-group and the pancreatic sub-group. He is a member of the Cancer Research UK Clinical Trials Awards and Advisory Committee (CTAAC). He also holds advisory board membership for a number of drug companies, and is a member of the Cancer Immunology and Immunotherapy Centre’s advisory board.

 

Publications

Khanna S, Graef S, Mussai F, Thomas A, Wali N, Yenidunya BG, Yuan C, Morrow B, Zhang J, Korangy F, Greten TF, Steinberg SM, Stetler-Stevenson M, Middleton G, DeSanto C, Hassan R. Tumor-Derived GM-CSF Promotes Granulocyte Immunosuppression in Mesothelioma Patients. Clin Cancer Res. 2018 Jun 15;24(12):2859-2872. doi:10.1158/1078-0432.CCR-17-3757. Epub 2018 Mar 30.

 

Corcoran RB, André T, Atreya CE, Schellens JHM, Yoshino T, Bendell JC, Hollebecque A, McRee AJ, Siena S, Middleton G, Muro K, Gordon MS, Tabernero J, Yaeger R, O’Dwyer PJ, Humblet Y, De Vos F, Jung AS, Brase JC, Jaeger S, Bettinger S, Mookerjee B, Rangwala F, Van Cutsem E. Combined BRAF, EGFR, and MEK Inhibition in Patients with BRAF(V600E)-Mutant Colorectal Cancer. Cancer Discov. 2018Apr;8(4):428-443. doi: 10.1158/2159-8290.CD-17-1226. Epub 2018 Feb 5.

 

Middleton G, Gridelli C, De Marinis F, Pujol JL, Reck M, Ramlau R, Parente B,  Pieters T, Visseren-Grul CM, San Antonio B, John WJ, Zimmermann AH, Chouaki N, Paz-Ares L. Evaluation of changes in renal function in PARAMOUNT: a phase III study of maintenance pemetrexed plus best supportive care versus placebo plus best supportive care after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. Curr Med Res Opin. 2018 May;34(5):865-871. doi: 10.1080/03007995.2018.1439462. Epub 2018 Mar 27

 

Ghafoor Q, Baijal S, Taniere P, O’Sullivan B, Evans M, Middleton G. Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors and Non-Small Cell Lung Cancer (NSCLC) – Advances in Molecular Diagnostic Techniques to Facilitate Targeted Therapy. Pathol Oncol Res. 2017 Dec 21. doi: 10.1007/s12253-017-0377-1. [Epub ahead of print] Review.

 

Lal N, White BS, Goussous G, Pickles O, Mason MJ, Beggs AD, Taniere P, Willcox BE, Guinney J, Middleton GW. KRAS Mutation and Consensus Molecular Subtypes 2 and 3 Are Independently Associated with Reduced Immune Infiltration and Reactivity in Colorectal Cancer. Clin Cancer Res. 2018 Jan 1;24(1):224-233. doi:10.1158/1078-0432.CCR-17-1090. Epub 2017 Oct 23.

 

Lal N, Willcox CR, Beggs A, Taniere P, Shikotra A, Bradding P, Adams R, Fisher D, Middleton G, Tselepis C, Willcox BE. Endothelial protein C receptor is overexpressed in colorectal cancer as a result of amplification and hypomethylation of chromosome 20q. J Pathol Clin Res. 2017 Jul 14;3(3):155-170. doi: 10.1002/cjp2.70. eCollection 2017 Jul.

 

Middleton G, Palmer DH, Greenhalf W, Ghaneh P, Jackson R, Cox T, Evans A, Shaw VE, Wadsley J, Valle JW, Propper D, Wasan H, Falk S, Cunningham D, Coxon F, Ross P, Madhusudan S, Wadd N, Corrie P, Hickish T, Costello E, Campbell F, Rawcliffe C, Neoptolemos JP. Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial. Lancet Oncol. 2017 Apr;18(4):486-499. doi: 10.1016/S1470-2045(17)30084-0.

 

Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O’Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW; European Study Group for Pancreatic Cancer. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017 Mar 11;389(10073):1011-1024. doi: 10.1016/S0140-6736(16)32409-6. Epub 2017 Jan 25.

 

Hiley CT, Le Quesne J, Santis G, Sharpe R, de Castro DG, Middleton G, Swanton C. Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease. Lancet. 2016 Sep 3;388(10048):1002-11. doi:10.1016/S0140-6736(16)31340-X. Epub 2016 Sep 1. Review.

 

Middleton G, Greenhalf W, Costello E, Shaw V, Cox T, Ghaneh P, Palmer DH, Neoptolemos JP. Immunobiological effects of gemcitabine and capecitabine combination chemotherapy in advanced pancreatic ductal adenocarcinoma. Br J Cancer. 2016 Mar 1;114(5):510-8. doi: 10.1038/bjc.2015.468. Epub 2016 Feb 4.