Overview
Cardiotoxicity affects 1 in 10 cancer patients receiving treatments such as chemotherapy, TKIs, checkpoint inhibitors, or CAR-T therapy. Combination regimens increase this risk, often forcing clinicians to compromise cancer therapy to protect heart health. Yet, the molecular mechanisms driving cancer drug-induced cardiotoxicity (cDIT) remain poorly understood, and no early diagnostic tools or targeted interventions currently exist.
About this opportunity
Our preliminary mass spectrometry data reveal unique protein fingerprints in patients with drug-induced heart injury, highlighting key pathways in cardiovascular stress and blood pressure regulation. These findings open the door to discovering new biomarkers and developing more effective ways to monitor patients in real-time.
We hypothesise that longitudinal profiling of patient-derived cardiac and vascular cells, treated with clinically relevant drug regimens, will identify early signalling events and novel biomarkers of cardiotoxicity. Embedding these biomarkers into a multiplex point-of-care (POC) device could enable real-time monitoring and personalised cardio-oncology care.
Aims
- Identify early molecular mechanisms that precede drug-induced cardiotoxicity.
- Develop and optimise a low-cost multiplex biosensor for cardiotoxicity detection.
- Validate the device using plasma samples from cancer patients receiving high-risk therapies.
Experimental Approach
- Mechanistic profiling: Induced pluripotent stem cell (iPSC) derived cardiomyocytes and endothelial cells (from individuals with and without cDIT) will be exposed to clinically relevant chemotherapy dosing regimens.
- Proteomic analysis: Longitudinal collection of conditioned media will enable quantitative mass spectrometry, ELISA, and bioinformatic pathway analysis to identify conserved, early biomarkers of toxicity.
- Functional assessment: Cellular contractility, calcium flux, mitochondrial health, and viability will be monitored to link molecular changes with functional impairment.
- Device development: Working with engineers, biomarkers will be embedded into a patented electrochemical biosensor platform initially validated for troponin. The multiplex design will be iteratively refined to incorporate novel biomarkers identified in vitro.
- Clinical validation: Archived and prospectively collected plasma samples will test device sensitivity, specificity, and predictive value against gold-standard hospital assays.
Novelty and Impact
This project bridges mechanistic biology with clinical translation and bioengineering. By embedding early cardiotoxicity biomarkers into a portable diagnostic device, this work aims to revolutionise real-time monitoring in cancer patients, enabling safer and more personalised treatment strategies.
The student will gain interdisciplinary expertise spanning cellular culture, proteomics, bioinformatics, and biosensor engineering — an exceptional skillset for careers in academic, clinical, or biotech research.
Training and Environment
You will join a vibrant MRC DiMeN interdisciplinary training environment, with opportunities to collaborate across cardiology, oncology, proteomics, and bioengineering groups. The project offers hands-on training in:
- Stem cell differentiation using iPSCs
- Biosensor design
- Clinical validation
You will also get training in transferable skills such as giving oral presentations, data analysis, scientific writing and coding.
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of-the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, training opportunities or internships in science policy, science communication and beyond.
Further reading
1. Lyon, A. R. et al. Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society. Eur J Heart Fail 22, 1945-1960 (2020). https://doi.org/10.1002/ejhf.1920
2. Tomlinson, L. et al. Attenuation of doxorubicin-induced cardiotoxicity in a human in vitro cardiac model by the induction of the NRF-2 pathway. Biomedicine & Pharmacotherapy 112, 108637 (2019). https://doi.org/https://doi.org/10.1016/j.biopha.2019.108637
3. Arjun, A. M. et al. Low-Cost Polyphenol–Polypyrrole Molecularly Imprinted Sensor for Point-of-Care Alzheimer’s Detection. ACS Sensors (2025). https://doi.org/10.1021/acssensors.5c01816
4. Deshpande, S., Arjun, A. M., Liu, G., Pawlak, K. & Sharma, S. Redox-Active Polyphenol Red Molecularly Imprinted Polymers on Porous Gold Electrodes for Ultrasensitive, AI-Assisted Detection of Alzheimer’s Biomarkers in Undiluted Biofluids. Advanced Healthcare Materials n/a, e03155 https://doi.org/https://doi.org/10.1002/adhm.202503155