Network Modelling

Predicting Personalised Therapeutic Combinations in Non-Small Cell Lung Cancer Using In Silico Modelling
The disease burden from non-small cell lung cancer (NSCLC) adenocarcinoma is substantial, with around a million new cases diagnosed …
Matthew A. Clarke, Charlie George Barker, Ashley Nicholls, Matt P. Handler, Lisa Pickard, Amna Shah, David Walter, Etienne De Braekeleer, Udai Banerji, Jyoti Choudhary, Saif Ahmed, Ultan McDermott, Gregory J. Hannon, Jasmin Fisher
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Predicting Personalised Therapeutic Combinations in Non-Small Cell Lung Cancer Using In Silico Modelling
Combination therapy
Computatational modelling allows screening of thousands of combinations of drugs to find the most effective treatments. This allows for better protection against the emergence of resistance, as well as rapid drug repurposing e.g. to combat emerging diseases such as COVID-19.
Matthew A. Clarke
Kreuzaler & Clarke et al. (2019) Kreuzaler & Clarke et al. (2019) Howell, Clarke & Reuschl et al. (2022) Howell, Clarke & Reuschl et al. (2022) Howell & Davies et al. (2023) Howell & Davies et al. (2023) Clarke, Barker & Nicholls et al. (2025)
Combination therapy
DNA Damage Repair and Radiotherapy
Cancers often emerge, in part, due to deficencies in DNA damage repair, making them vulnerable to DNA damaging treatments such as radiotherapy. While radiotherapy efficacy has been increasing, this is mainly due to better targeting of tumour anatomy, but targeted therapy offers the opportunity to radiosensitise tumour cells by targeting vulnerabilities in the tumour biology. We use computational modelling to find such vulnerabilities, and explore potential resistance mechanisms.
Matthew A. Clarke
Clarke, Barker & Nicholls et al. (2025)
DNA Damage Repair and Radiotherapy
HOXA9 has the hallmarks of a biological switch with implications in blood cancers
Blood malignancies arise from the dysregulation of haematopoiesis. The type of blood cell and the specific order of oncogenic events …
Laure Talarmain, Matthew A. Clarke, David Shorthouse, Lilia Cabrera-Cosme, David G. Kent, Jasmin Fisher, Benjamin A. Hall
PDF Code Dataset Project DOI
HOXA9 has the hallmarks of a biological switch with implications in blood cancers
Executable cancer models: successes and challenges
Making decisions on how best to treat cancer patients requires the integration of different data sets, including genomic profiles, …
Matthew A. Clarke, Jasmin Fisher
PDF DOI
Executable cancer models: successes and challenges
Heterogeneity of Myc expression in breast cancer exposes pharmacological vulnerabilities revealed through executable mechanistic modeling
Cells with higher levels of Myc proliferate more rapidly and supercompetitively eliminate neighboring cells. Nonetheless, tumor cells …
Peter Kreuzaler, Matthew A. Clarke, Elizabeth J. Brown, Catherine H. Wilson, Roderik M. Kortlever, Nir Piterman, Trevor Littlewood, Gerard I. Evan, Jasmin Fisher
PDF Dataset Project DOI
Heterogeneity of Myc expression in breast cancer exposes pharmacological vulnerabilities revealed through executable mechanistic modeling
Predictive Computational Modelling of the c-myc Gene Regulatory Network for Combinatorial Treatments of Breast Cancer
As cancer tumours develop, competition between cells will favour those with some mutations over others, creating a dynamic …
Matthew A. Clarke
PDF DOI
Predictive Computational Modelling of the c-myc Gene Regulatory Network for Combinatorial Treatments of Breast Cancer