The NCRI Lung Group brings together clinicians, scientists and patients, carers and others affected by cancer (also known as ‘consumers’), amongst many others, to coordinate the development of a strategic portfolio of research within the field of lung cancer. The group works closely with clinical research networks, funders and researchers to develop research to improve outcomes for lung cancer patients.  

The NCRI Lung Group consists of an executive group, chaired by Prof Gary Middletonwhich provides oversight of the research landscape and proactively identifies opportunities for the group. The NCRI Lung Group also has several subgroups that develop research in areas of strategic need.

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Group members

Prof Gary Middleton

Chair

Prof Gary Middleton is a clinical academic with a clinical practice in thoracic and colorectal ca ...

Prof Gary Middleton

Chair

Prof Gary Middleton is a clinical academic with a clinical practice in thoracic and colorectal cancer and an active lab programme. He is the Chief Investigator, National Lung Matrix Trial (NLMT). This is the flagship lung cancer CR-UK funded stratified medicine trial aligned to the national Stratified Medicine Programme 2. The trial was highlighted in the recent DHSS document ‘Saving and Improving Lives: The Future of UK Clinical Research Delivery’ as a trial that “shows the power of collaboration, through the UK’s integrated health research System”. It is the largest and most ambitious signal of activity study examining potential genotype matched targeted therapies in lung cancer globally. Data from 19 biomarker:drug cohorts was presented in the Presidential Symposium at the World Lung Cancer Conference, 2019 and published in Nature, 2020 (Middleton G, et al. The National Lung Matrix Trial of personalized therapy in lung cancer. Nature. 2020 Jul;583(7818):807-812). There are several further high impact papers to come from this trial which will incorporate the large ctDNA analysis from this study. In particular these include the results from the palbociclib treated patients where the ctDNA analysis of KRAS mutant patients will be mapped to the results of transgenic models of KRAS mutant lung cancer in which multiple barcoded genes are knocked down with CRISPR to identify concomitant sensitising or resistance aberrations in collaboration with D2G (Stanford).

It is clear from the outputs of NLMT that the genomic context of targeted genomic aberrations, the degree of genomic complexity and instability, are critically important in determining the outcome with genotype-matched targeted therapies (Middleton G. Towards personalized treatment of smoking related lung cancers. Nature. 2021 Jun 18. doi: 10.1038/d41586-021-01113-90). The learnings from the trial have led to a key publication which represents a blueprint for future precision medicine trials in cancer (Middleton G, et al. A state-of-the-art review of stratified medicine in cancer: towards a future precision medicine strategy in cancer. Ann Oncol. 2022 Feb;33(2):143-157). In part this is explicitly a call for a more contextualised stratified medicine, one which takes into account the genomic, transcriptional and immunobiological context on which the targeted genomic aberration is inscribed. It builds on important work on how the transcriptional and immunological landscape of canonical oncogenic drivers shapes both biology and response to targeted therapy (Middleton G, et al. BRAF-mutant Transcriptional Subtypes Predict Outcome of Combined BRAF, MEK, and EGFR Blockade with Dabrafenib, Trametinib, and Panitumumab in Patients with Colorectal Cancer. Clin Cancer Res. 2020 Feb 11. pii: clincanres.3579.2019 and Lal N, White BS, Goussous G, Pickles OJ, Mason M, Beggs AD, Taniere P, Willcox BE, Guinney J, Middleton G. 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). This concept of target context as supplemental biomarker for outcome forms the key translational component of the CR UK sponsored DETERMINE trial in which WGS and RNAseq will be performed to establish the impact on outcome with genotype matched-therapies of the genomic, transcriptomic and immunological context on which the targeted aberrations are inscribed . It is also a superb opportunity to discover novel targets in rare and paediatric cancers in both the exome and in the non-coding genome where we will analyse alternative polyadenylation, pseudogenes and somatic non-coding mutations in regulatory regions. Middleton is translational lead of the DETERMINE trial which will commence recruitment later this year with the translational work being performed in Birmingham.

As a result of NLMT it is also apparent that squamous lung cancer is not susceptible to genotype matched targeted therapy and that other approaches are needed for this disease of huge unmet therapeutic need. Middleton is leading on KETO-LUNG, a feasibility trial exploring the addition of a ketogenic diet to standard chemo-immunotherapy in LUSC, to harness the unique metabolic vulnerability of squamous lung cancer (a strict reliance on anabolic glycolysis for the provision of redox potential). This trial in effect inaugurates metabolic Precision Medicine – stratification for metabolic intervention by histology. We have huge buy-in from the ECMC and the expertise of our ECMCs will be integral to the successful prosecution of this complex intervention trial. The trial design is an exemplar of PPI and our PPI rep is a co-investigator. We will analyse metabolic and redox shifts using tumoral 13C tracing at the Metabolic Tracer Analysis Core at the University of Birmingham (Tennant) for the first time in any clinical trial in advanced disease using biopsy samples. This technology could prove invaluable to other metabolic intervention trials being run across the network.

Middleton is Chief Investigator, PePS2: A phase II study of pembrolizumab in patients with advanced non-small lung cancer and a performance status of 2. This is the first ever study to prospectively assess the activity of anti-PD-1 agents in patients with PS2 and thus is of pivotal importance in opening up such therapies to a large number of patients. Results were presented at ESMO, 2018 and published in Lancet Respiratory Medicine in 2020 (Middleton G, et al. Pembrolizumab in patients with non-small-cell lung cancer of performancestatus 2 (PePS2): a single arm, phase 2 trial. Lancet Respir Med. 2020 Mar 19:S2213-2600(20)30033-3.) and are being used to seek CDF approval for this pembrolizumab in this large group of lung cancer patients with huge unmet therapeutic need.

Of potentially huge impact is the recent work from the Middleton group looking at predictive biomarkers for immune related adverse events in lung cancer patients treated with checkpoint blockade. Using CyTOF and B cell functional assays we have demonstrated that patients developing severe toxicity have significant baseline qualitative and quantitative defects in B regulatory cells. The manuscript has been accepted for publication in Nature Communications. We have patent protection on this potentially crucial and game changing biomarker. We also have patent protection on a highly predictive autoantibody signature for outcome following resection of early stage lung cancer and are validating this data using TRACERx samples with a view to designing a trial of adjuvant vaccination against the candidate antigens which include a large proportion of ctAgs (Patel AJ, Tan TM, Richter AG, Naidu B, Blackburn JM, Middleton GW. A highly predictive autoantibody-based biomarker panel for prognosis in early-stage NSCLC with potential therapeutic implications. Br J Cancer. 2022 Feb;126(2):238-246.)

Anna Minchom

Dr Anna Minchom

Deputy Chair

Dr Anna Minchom is a Consultant Medical Oncologist and BRC Clinical Scientist in the Lung Unit an ...

Dr Anna Minchom

Deputy Chair

Dr Anna Minchom is a Consultant Medical Oncologist and BRC Clinical Scientist in the Lung Unit and the Drug Development Unit at the Royal Marsden Hospital and a team leader at the Institute of Cancer Research.

Dr Minchom completed her undergraduate medical training in the University of Wales College of Medicine, qualifying in 2003. She was awarded MRCP in 2008. She trained in medical oncology at the Royal Marsden Hospital during which time she completed laboratory research investigating mechanisms of resistance to targeted drugs in non-small cell lung cancer, for which she was awarded an MD(res).

Dr Minchom is principal investigator on early phase drug trials including first-in-human clinical trials. Her main research focus is using a biomarker-driven and translational approach to develop novel drugs and drug combinations for the treatment of patients with lung cancer and mesothelioma.

Crispin Hiley

Dr Crispin Hiley

Deputy Chair

Dr Crispin Hiley is an Associate Professor with tenure in Radiation Oncology at UCL and an Honora ...

Dr Crispin Hiley

Deputy Chair

Dr Crispin Hiley is an Associate Professor with tenure in Radiation Oncology at UCL and an Honorary Consultant Clinical Oncologist at UCLH.

He graduated with honours from the University in Manchester in 2005. He has trained in Oncology at many centres of excellence both in the UK and aboard. These include the Christie Hospital, the MD Anderson Cancer Centre (Houston, USA), Kings College (NIHR Clinical Lecturer) and the Royal Marsden (NIHR Clinical Fellow). He completed a PhD at the University of London with the Barts Cancer Institute and a postdoctoral research Fellowship the Francis Crick Institute and the UCL Cancer institute.

He became a consultant in 2018 joining the thoracic oncology team at UCLH. In addition, he is the UCLH Lead for Lung Proton Therapy, Deputy Lead of Clinical Trials Theme for the CRUK Lung Cancer Centre of Excellence and NIHR Clinical Research Network Speciality Research Lead Radiotherapy for North London. He heads a research group at the UCL Cancer Institute focused on understanding resistance to radiation therapy.

Dr Hiley specialises in non-surgical treatments for all types of lung cancer. He has expertise in chemotherapy, immunotherapy and radiotherapy including state of the art radiotherapy techniques including Volumetric Arc Therapy (VMAT), Intensity Modulated Radiotherapy (IMRT), Image Guided Radiotherapy (IGRT), Proton Therapy and Stereotactic Radiotherapy (SBRT). Dr Hiley has expertise in treating all sites of metastatic disease (except for brain) with stereotactic radiotherapy including lung, liver, lymph nodes, adrenal glands, spine and other bone sties.

He is the principal investigator and national chief investigator for several academic and commercial clinical trials in lung cancer. He has published in several the world’s leading journals including NEJM, The Lancet, Nature and Cell. He is a member of the expert group which authored the Radiotherapy for Lung Cancer Royal College of Radiologists Consensus Statement.