Article highlights & insights
Although small cell lung cancer (SCLC) is treated as a homogeneous disease, biopsies and preclinical models reveal heterogeneity in transcriptomes and morphology. SCLC subtypes were recently defined by neuroendocrine transcription factor (NETF) expression. Circulating-tumour-cell-derived explant models (CDX) recapitulate donor patients’ tumour morphology, diagnostic NE marker expression and chemotherapy responses. We describe a biobank of 38 CDX models, including six CDX pairs generated pretreatment and at disease progression revealing complex intra- and intertumoral heterogeneity. Transcriptomic analysis confirmed three of four previously described subtypes based on ASCL1, NEUROD1 and POU2F3 expression and identified a previously unreported subtype based on another NETF, ATOH1. We document evolution during disease progression exemplified by altered MYC and NOTCH gene expression, increased ‘variant’ cell morphology, and metastasis without strong evidence of epithelial to mesenchymal transition. This CDX biobank provides a research resource to facilitate SCLC personalised medicine.
Although small cell lung cancer (SCLC) is treated as a homogeneous disease, biopsies and preclinical models reveal heterogeneity in transcriptomes and morphology. SCLC subtypes were recently defined by neuroendocrine transcription factor (NETF) expression. Circulating-tumour-cell-derived explant models (CDX) recapitulate donor patients’ tumour morphology, diagnostic NE marker expression and chemotherapy responses. We describe a biobank of 38 CDX models, including six CDX pairs generated pretreatment and at disease progression revealing complex intra- and intertumoral heterogeneity. Transcriptomic analysis confirmed three of four previously described subtypes based on ASCL1, NEUROD1 and POU2F3 expression and identified a previously unreported subtype based on another NETF, ATOH1. We document evolution during disease progression exemplified by altered MYC and NOTCH gene expression, increased ‘variant’ cell morphology, and metastasis without strong evidence of epithelial to mesenchymal transition. This CDX biobank provides a research resource to facilitate SCLC personalised medicine.
Institute Authors
Group leader
Labs & Facilities
Research topics & keywords
Meet the Research Team
Senior Group Leader
Team Lead
Postdoctoral Scientist
PhD Student
PhD Student
Associate Scientist
Postdoctoral Scientist
PhD Student
PhD Student
All publications
https://doi.org/10.1136/jitc-2025-012527
Systemic immunosuppression from ultraviolet radiation exposure inhibits cancer immunotherapy
31 October 2025
Institute Authors (4)
Isabella Mataloni, Antonia Banyard, Garry Ashton, Amaya Virós
Labs & Facilities
Mass and Flow Cytometry, Histology
Research Group
Skin Cancer & Ageing
31 October 2025
https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-24-1224/766638/Glucocorticoids-Unleash-Immune-dependent-Melanoma
Glucocorticoids Unleash Immune-dependent Melanoma Control through Inhibition of the GARP/TGF β Axis
15 October 2025
Institute Authors (12)
Charles Earnshaw, Poppy Dunn, Shih-Chieh Chiang, Maria Koufaki, Massimo Russo, Kimberley Hockenhull, Erin Richardson, Anna Pidoux, Alex Baker, Richard Reeves, Robert Sellers, Sudhakar Sahoo
Labs & Facilities
Computational Biology Support, Visualisation, Irradiation and Analysis
Research Group
Cancer Inflammation and Immunity
15 October 2025
/wp-content/uploads/2025/09/Annual_Report_2024.pdf
2024 Annual Report
23 September 2025
23 September 2025
https://doi.org/10.1182/blood.2024028033
An in vivo barcoded CRISPR-Cas9 screen identifies Ncoa4-mediated ferritinophagy as a dependence in Tet2-deficient hematopoiesis
4 September 2025
Institute Authors (1)
Justin Loke
Research Group
Myeloid Cancer Biology
4 September 2025
https://doi.org/10.1038/s41467-024-49692-1
Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma
15 July 2025
Institute Authors (1)
Samra Turajlić
Research Group
Cancer Dynamics
15 July 2025
https://doi.org/10.1038/s41420-025-02582-x
Mutant p53 induces SH3BGRL expression to promote cell engulfment
1 July 2025
Institute Authors (5)
Garry Ashton, John Weightman, Wolfgang Breitwieser, Sudhakar Sahoo, Antonia Banyard
Labs & Facilities
Computational Biology Support, Mass and Flow Cytometry, Molecular Biology
1 July 2025
Our Research
Our research spans the whole spectrum of cancer research from cell biology through to translational and clinical studies
Research Groups
Our research groups study many fundamental questions of cancer biology and treatment
Our Facilities
The Institute has outstanding core facilities that offer cutting edge instruments and tailored services from expert staff
Latest News & Updates
Find out all our latest news
Careers that have a lasting impact on cancer research and patient care
We are always on the lookout for talented and motivated people to join us. Whether your background is in biological or chemical sciences, mathematics or finance, computer science or logistics, use the links below to see roles across the Institute in our core facilities, operations teams, research groups, and studentships within our exceptional graduate programme.
Institute life in Manchester
We strive to make our community a welcoming, caring and enthusiastic one, fuelling ambition with opportunities for training and mentoring to help us all achieve our personal and professional goals.
“We are so pleased to have received the funding to enable us to test our hypothesis in the lab. If we can create a new medicine that can precisely target a specific type of cell within the tumour, and restore anti-cancer immune responses, this will be a game-changer for oesophageal cancer patients “
Sara Valpione
Former Institute Clinical Fellow and now Clinician in Residence within the CRUK National Biomarker Centre
“My charity bake sales – known as “David’s Great British Bake Off” – are always a hit, home baked products taste so much better than shop bought and are greatly appreciated by staff!”
David Jenkins
Purchasing Officer
“We’ve seen some remarkable responses, with an improvement for some patients within days. This is an early phase trial so there’s a lot more work to do. But the data we have so far is very encouraging and could help many thousands of people in the future”
Tim Somervaille
Senior Group Leader
“It is a pleasure to introduce my team who work to deliver our research goals. We work in a friendly and collaborative environment, supporting each other’s projects. “
Amaya Virós
CRUK Advanced Clinician Scientist Fellow
“We are so pleased to have received the funding to enable us to test our hypothesis in the lab. If we can create a new medicine that can precisely target a specific type of cell within the tumour, and restore anti-cancer immune responses, this will be a game-changer for oesophageal cancer patients “
Sara Valpione
Former Institute Clinical Fellow and now Clinician in Residence within the CRUK National Biomarker Centre
“My charity bake sales – known as “David’s Great British Bake Off” – are always a hit, home baked products taste so much better than shop bought and are greatly appreciated by staff!”
David Jenkins
Purchasing Officer
“We’ve seen some remarkable responses, with an improvement for some patients within days. This is an early phase trial so there’s a lot more work to do. But the data we have so far is very encouraging and could help many thousands of people in the future”
Tim Somervaille
Senior Group Leader
“It is a pleasure to introduce my team who work to deliver our research goals. We work in a friendly and collaborative environment, supporting each other’s projects. “
Amaya Virós
CRUK Advanced Clinician Scientist Fellow