Optimising cancer therapy

The project will examine optimisation of drug therapies that target cell division and create DNA damage, specifically the exposure to the drug can be modulated by an infusion device during the circadian cycle thereby reducing toxicity to
normal cells whilst remaining effective against cancer cells. To determine optimal therapy design, the Pontryagin's maximum principle - PMP can be used, where the function to be optimised includes also a periodic toxicity cost to
normal cells. The models will be developed in collaboration with the external partner.
The project aims to develop a new optimisation framework for emerging cancer therapies, across a range of treatments/drugs at both a personalised and standard therapy levels. We aim to develop optimal therapies for a number of specific cancers and drugs.
Although optimal control theory has been applied widely to cancer since the 1980s, emerging therapies and increasingly detailed drug mechanisms enable more applicable models and optimisation conditions to be utilised. The PhD is
particular novel in the focus on chronotherapy, ie the nonautonomous nature of the dynamics and PMP.
Recent experimental and clinical results support the need of personalising the chronomodulated administration pattern according to the patient genetic and circadian profile. This project will contribute to new approaches of cancer
treatment according to the circadian rhythm of the patient.

The proposed projects falls within mathematical science and physics with an application focus on quantitative biomedical research.

Research areas; Healthcare technologies, Mathematical Sciences, Physical Sciences
External Partner; Institute Curie Research Center, INSERM unit U900, Systems Pharmacology to personalize Anticancer Therapies (SYSPHARMA) team

In the 2018 Government Office for Science report, 'Computational Modelling: Technological Futures', Greg Clarke, the Secretary of State for Business Energy and Industrial Strategy, wrote "Computational modelling is essential to our future productivity and competitiveness, for businesses of all sizes and across all sectors of the economy". With its focus on computational models, the mathematics that underpin them, and their integration with complex data, the MathSys II CDT will generate diverse impacts beyond academia. This includes impacts on skills, on the economy, on policy and on society.

Impacts on skills.
MathSys II will produce a minimum of 50 PhD graduates to support the growing national demand for advanced mathematical modelling and data analysis skills. The CDT will provide each of them with broad core skills in the MSc, a deep knowledge of their chosen research specialisation in the PhD and a complementary qualification in transferable skills integrated throughout. Graduates will thus acquire the profiles needed to form the next generation of leaders in business, government and academia. They will be supported by an integrated pastoral support framework, including a diverse group of accessible leadership role models. The cohort based environment of the CDT provides a multiplier effect by encouraging cohorts to forge long-lasting professional networks whose value and influence will long outlast the CDT itself. MathSys II will seek to maximise the influence of these networks by providing topical training in Responsible Research and Innovation, by maintaining a robust Equality, Diversity & Inclusion policy, and by integration with Warwick's global network of international partnerships.

Economic impacts.
The research outputs from many MathSys II PhD projects will be of direct economic value to commercial, public sector and charitable external partners. Engagement with CDT partners will facilitate these impacts. This includes co-supervision of PhD and MSc projects, co-creation of Research Study Groups, and a strong commitment to provide placements/internships for CDT students. When commercial innovations or IP are generated, we will work with Warwick Ventures, the commercial arm of the University of Warwick, to commercialise/license IP where appropriate. Economic impact may also come from the creation of new companies by CDT graduates. MathSys II will present entrepreneurship as a viable career option to students. One external partner, Spectra Analytics, was founded by graduates of the preceding Complexity Science CDT, thus providing accessible role models. We will also provide in-house entrepreneurship training via Warwick Ventures and host events by external start-up accelerator Entrepreneur First.

Impacts on policy.
The CDT will influence policy at the national and international level by working with external partners operating in policy. UK examples include Department of Health, Public Health England and DEFRA. International examples include World Health Organisation (WHO) and the European Commission for the Control of Foot-and-mouth Disease (EuFMD). MathSys students will also utilise the recently announced UKRI policy internships scheme.

Impacts on society.
Public engagement will allow CDT students to promote the value of their research to society at large. Aside from social media, suitable local events include DataBeers, Cafe Scientifique, and the Big Bang Fair. MathSys will also promote a socially-oriented ethos of technology for the common good. Concretely, this includes the creation of open-source software, integration of software and data carpentry into our computational and data driven research training and championing open-access to research. We will also contribute to the 'innovation culture and science' strand of Coventry's 2021 City of Culture programme.