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, School of Cancer Sciences, 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.

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 Dr Mark Cobbold and 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

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

Annels NE, Shaw VE, Gabitass RF, Billingham L, Corrie P, Eatock M, Valle J, Smith D, Wadsley J, Cunningham D, Pandha H, Neoptolemos JP, Middleton G. The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with advanced pancreatic cancer. Cancer Immunol Immunother. 2014 Feb;63(2):175-83.

Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86.

Middleton G, Brown S, Lowe C, Maughan T, Gwyther S, Oliver A, Richman S, Blake D, Napp V, Marshall H, Wadsley J, Maisey N, Chau I, Hill M, Gollins S, Myint S, Slater S, Wagstaff J, Bridgewater J, Seymour M. A randomised phase III trial of the pharmacokinetic biomodulation of irinotecan using oral ciclosporin in advanced colorectal cancer: results of the Panitumumab, Irinotecan & Ciclosporin in COLOrectal cancer therapy trial (PICCOLO). Eur J Cancer. 2013 Nov;49(16):3507-16.

Okines AF, Gonzalez de Castro D, Cunningham D, Chau I, Langley RE, Thompson LC, Stenning SP, Saffery C, Barbachano Y, Coxon F, Middleton G, Ferry D, Crosby T, Madhusudan S, Wadsley J, Waters J, Hall M, Swinson D, Robinson A, Smith D, Reis-Filho JS, Waddell TS, Puckey L, Hulkki Wilson S, Eltahir Z, Band M, Wotherspoon A. Biomarker analysis in oesophagogastric cancer: Results from the REAL3 and TransMAGIC trials. Eur J Cancer. 2013 Jun;49(9):2116-25.

Seymour MT, Brown SR, Middleton G, Maughan T, Richman S, Gwyther S, Lowe C, Seligmann JF, Wadsley J, Maisey N, Chau I, Hill M, Dawson L, Falk S, O’Callaghan  A, Benstead K, Chambers P, Oliver A, Marshall H, Napp V, Quirke P. Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. Lancet Oncol. 2013 Jul;14(8):749-59.

Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, Wotherspoon A, Saffery C, Middleton G, Wadsley J, Ferry D, Mansoor W, Crosby T, Coxon F, Smith D, Waters J, Iveson T, Falk S, Slater S, Peckitt C, Barbachano Y. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):481-9.  Erratum in: Lancet Oncol. 2013 Jun;14(7):e254. Frances, Alicia [corrected to Okines, Alicia Frances Clare]. PubMed PMID: 23594787; PubMed Central PMCID: PMC3669518.

Ward ST, Weston CJ, Hepburn E, Damery S, Hejmadi RK, Morton DG, Middleton G, Ismail T, Adams DH. Evaluation of serum lysyl oxidase as a blood test for colorectal cancer. Eur J Surg Oncol. 2013 Nov 6. pii: S0748-7983(13)00871-8.

Lee SM, Khan I, Upadhyay S, Lewanski C, Falk S, Skailes G, Marshall E, Woll PJ, Hatton M, Lal R, Jones R, Toy E, Chao D, Middleton G, Bulley S, Ngai Y, Rudd  R, Hackshaw A, Boshoff C. First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2012 Nov;13(11):1161-70.

Middleton GW, Annels NE, Pandha HS. Are we ready to start studies of Th17 cell manipulation as a therapy for cancer? Cancer Immunol Immunother. 2012 Jan;61(1):1-7.

Wakelee HA, Takimoto CH, Lopez-Anaya A, Chu Q, Middleton G, Dunlop D, Ramlau  R, Leighl N, Rowinsky EK, Hao D, Zatloukal P, Jacobs CD, Rodon J. The effect of bexarotene on atorvastatin pharmacokinetics: results from a phase I trial of bexarotene plus chemotherapy in patients with advanced non-small cell lung cancer. Cancer Chemother Pharmacol. 2012 Feb;69(2):563-71.