Fitness costs of drug resistance in cancer

Supervisors

Objectives

Resistance to treatments often comes with a proliferative cost for cancer cells, which could be exploited in adaptive dosing schedules to manage resistance evolution. This project aims to quantify the fitness costs of drug resistance across a broad panel of cancer cell lines treated with standard therapies, providing data to support innovative treatment strategies. Specific objectives: • Conduct a large-scale screen to measure drug-resistance costs in cancer cell lines treated with standard-of-care drugs. • Analyse the relationship between fitness costs and resistance, identifying opportunities for adaptive dosing strategies. • Propose novel treatment strategies leveraging proliferative costs associated with resistance

Methodology

Experimental evolution applied to human cancer models
Single cell multiomic profiling
Computational genomics method development
Mathematical modelling of evolutionary dynamics

Required Skills

Ideally someone from a quantitative background (physics/maths/comp sci etc) who isn’t afraid to jump into the wet-lab. A keen interest in evolutionary dynamics is essential!

Expected Results

The project will generate comprehensive data on drug-resistance costs in cancer, offering insights into adaptive treatment strategies. These findings could guide the development of therapies that exploit the fitness costs of resistance, potentially improving patient outcomes with existing cancer drugs.

Planned Secondments

UCAM (Blundell) months 19-20 (2 months) to receive training on modelling clonal evolution in cancer.

CUT (Lakatos) month 23 (2 weeks) to receive complementary training mathematical modelling.

CRG (Irimia) month 24 (2 weeks) to learn transcriptomic analyses in the context of protective cancer signatures and their relationship with resistance.

Enrolment in doctoral programs

Institute of Cancer Research, London, UK

References

https://www.nature.com/articles/s41467-025-59479-7
https://www.nature.com/articles/s43018-025-00955-w
https://www.nature.com/articles/s41586-024-07747-9
https://www.nature.com/articles/s41586-022-05311-x
https://www.nature.com/articles/s41586-022-05202-1