Program Overview

Introduction to the PhD Program

The Institute of Cancer Research (ICR) offers a PhD program in cancer research, providing students with the opportunity to work on cutting-edge projects and contribute to the advancement of cancer treatment.

PhD Projects

The ICR offers a range of PhD projects, including:

• New strategies for exploiting the fitness costs of drug resistance in cancer
• Adaptive therapy for cancer treatment
• Evolutionary dynamics of cancer resistance

Project Background

The project "New strategies for exploiting the fitness costs of drug resistance in cancer" aims to systematically characterize the mechanisms and fitness costs of resistance by performing a large-scale experimental screen across diverse cancer cell lines exposed to a range of standard-of-care drugs.

Project Aims

The project aims to:

• Barcode a panel of cancer cell lines to enable genetic lineage tracing
• Design a large-scale experimental screen in which clinically relevant drugs are applied to barcoded cancer cell lines, generating resistant clones in vitro
• Use single cell DNA sequencing to track genetic lineages through treatment and resistance, and single cell RNA sequencing to characterize the resistant phenotype
• Apply mathematical frameworks to learn the dynamics of resistance evolution
• Combine experimental results with computational modelling of evolutionary dynamics to propose new therapeutic strategies for adaptive intervention

Further Details and Requirements

The project requires a strong interest in experimental cancer biology, and prior wet-lab training is not essential. Experience with computational or mathematical modelling would be valuable. The student will generate data in the wet-lab to determine the cost of resistance in a large panel of cancer cell lines and patient-derived organoids, treated with a broad range of standard-of-care chemotherapies.

Candidate Profile

The ideal candidate will have a BSc (First or 2:1) or Master's degree, ideally in a quantitative subject (for example physics, mathematics, or computer science) but experience of cell or molecular biology is highly valued. A strong interest in experimental cancer biology is essential, but prior wet-lab training is not essential.

Literature References

The project is based on the following literature references:

• "A view on drug resistance in cancer" Vasan et al, Nature. 2019 Nov;575(7782):299-309. doi: 10.1038/s-1.
• "Life history trade-offs in cancer evolution" Aktipis et al, Nat Rev Cancer. 2013 Dec;13(12):883-92. doi: 10.1038
  rc3606.
• "Adaptive therapy" Gatenby et al, Cancer Res. 2009 Jun 1;69(11):. doi: 10.1158/.CAN-.
• "Adaptive Therapy Exploits Fitness Deficits in Chemotherapy-Resistant Ovarian Cancer to Achieve Long-Term Tumor Control" Hockings et al. Cancer Res. 2025 Sep 15;85(18):. doi: 10.1158/.CAN-.
• "Study protocol for Adaptive ChemoTherapy for Ovarian cancer (ACTOv): a multicentre phase II randomised controlled trial to evaluate the efficacy of adaptive therapy (AT) with carboplatin, based on changes in CA125, in patients with relapsed platinum-sensitive high-grade serous or high-grade endometrioid ovarian cancer" Mukerjee et al. BMJ Open. 2024 Dec 22;14(12):e. doi: 10.1136/bmjopen-.
• "Quantitative measurement of phenotype dynamics during cancer drug resistance evolution using genetic barcoding" Whiting et al, Nat Commun. 2025 Jun 20;16(1):5282. doi: 10.1038/s-7.

Research Environment

The studentship will be based in the Genomics and Evolutionary Dynamics group, within the Centre for Evolution and Cancer. The group has around 12 years of experience in both experimental and bioinformatic analyses of cancer evolution, and full training in both wet and dry lab techniques will be provided to the successful candidate.

International Secondments

The candidate will benefit from targeted international secondments, including:

• A two-month stay at the University of Cambridge (with Prof Jamie Blundell) to receive training in modelling clonal evolution in cancer
• A two-week stay at Chalmers University (Gothenburg, with Dr Eszter Lakatos) to receive complementary training in mathematical modelling
• A short secondment at the Centre for Genomic Regulation (Barcelona, with Prof Manuel Irimia) to focus on transcriptomic analyses in the context of protective cancer signatures and their relationship with resistance

Funding

The candidate will receive a monthly salary of Euros 4,917 (subject to tax and National Insurance deductions), which includes both a living allowance and a mobility allowance, for a duration of 36 months. Additionally, candidates with a family may be eligible for a monthly family allowance of Euros 380 (also subject to tax and National Insurance deductions), provided they meet the eligibility criteria for the MSCA family allowance. In the fourth year of the PhD, the candidate will receive the standard ICR stipend rate.