Understanding how tumours become radioresistant

Overview
Cancer treatment fails when tumours acquire or exploit biological mechanisms that enable survival after irradiation. Our research seeks to identify and understand these mechanisms, from hypoxia and altered signalling networks to DNA repair and tumour–microenvironment interactions. By revealing how resistance develops and evolves, we aim to identify measurable biomarkers and novel therapeutic targets that improve the precision and effectiveness of radiotherapy.

Focus Areas

• Hypoxia biology & therapy: Mechanisms, biomarkers, and gene‑directed strategies targeting hypoxic compartments.

• Resistance signaling: Notch, STAT5A, YB‑1 and other pathways that modulate radioresponse.

• DNA repair & dose‑response: Mismatch repair, MGMT/O6MeG, low‑dose hypersensitivity.

• Microenvironment & vesicles: Vascular and extracellular vesicle (EV) responses to RT.

• Radiosensitizers & modulators: Small molecules (e.g., metformin, statins, melatonin) to enhance RT response.

Flagship Publications (Selected)

• Concept & Mechanism

  • Hypoxia in prostate cancer: a powerful shield against tumour destruction?(Cancer Treat Rev, 2008) — Framing of hypoxia as a clinical resistance driver.

  • Time, location and function of hypoxia‑inducible factors are critical to therapeutic tumour response (BMJ Oncol, 2024) — Explores how HIF dynamics shape treatment sensitivity.

• Gene‑Directed Strategies

  • Hypoxia response element‑driven CD/5‑FC gene therapy enhances radiosensitivity in vitro(J Gene Med, 2009).

  • Tissue plasminogen activator promoter: a novel tool for radiogenic gene therapy (J Gene Med, 2008).

  • Radiation to control gene expression in tumors (Cancer Biol Ther, 2007).

• Resistance Signaling & miRNA

  • Notch, hypoxia signaling and prostate cancer (Nat Rev Urol, 2013) & Notch‑3 receptor: a molecular switch to tumorigenesis? (Cancer Treat Rev, 2017).

  • Multiplex profiling identifies clinically relevant signalling proteins in an isogenic prostate cancer model of radioresistance (Sci Rep, 2019).

  • miR‑31 modulates tumor sensitivity to radiation in esophageal cancer(J Mol Med, 2012); Low miR‑187 promotes resistance and correlates with failure (Mol Med, 2016).

• DNA Repair & Dose Response

  • MSH2 dictates survival after low‑dose radiation in endometrial carcinoma (Cancer Lett, 2013).

  • Recognition of O6MeG lesions… prerequisite for low‑dose radiation hypersensitivity (Radiat Res, 2009).

  • DNA mismatch repair and DDR to ionising radiation (Cancer Treat Rev, 2010).

• Microenvironment, EVs & Vascular

  • Vascular responses to RT and ADT in experimental prostate cancer (Radiat Oncol, 2012).

  • Extracellular vesicles and the “six Rs” in radiotherapy (Cancer Treat Rev, 2024).

• Theranostics & Radiomics

  • [64Cu][Cu(elesclomol)] as a theranostic for hypoxic solid tumours (EJNMMI, 2023).

  • Exploring hypoxia in prostate cancer with MRI radiomics & pimonidazole (Anticancer Res, 2023).

• Radiosensitizers & Modulators

  • Metformin and improved RT outcomes: review(Cancer Treat Rev, 2017).

  • Clinical potential of statins in prostate cancer RT (Anticancer Res, 2017).

  • Melatonin for breast cancer RT patients (Int J Radiat Biol, 2018).

Experimental platforms

We combine experimental radiobiology, molecular profiling, functional genomics, quantitative imaging and computational analysis to investigate tumour resistance across cellular, preclinical and clinical models.

Scientific contribution

• Established hypoxia as a measurable determinant of tumour radiation response.

• Defined signalling networks that contribute to radioresistance and treatment failure.

• Advanced biological imaging and molecular biomarkers of tumour resistance.

• Provided mechanistic foundations for novel radiosensitisation strategies.

Current questions

Despite major advances, important questions remain.

• How does tumour hypoxia interact with other mechanisms of radioresistance?

• Which resistance pathways are clinically actionable?

• Can functional biomarkers predict treatment failure before therapy begins?

Looking ahead

Understanding tumour resistance remains fundamental to improving radiotherapy. Building on two decades of work in hypoxia, signalling and DNA damage responses, we are now investigating how these mechanisms interact with newly emerging biological determinants of tumour behaviour, creating a more integrated understanding of radiation response.

Get Involved

• We welcome collaborations in hypoxia imaging, theranostic development, and mechanistic radiosensitization. Contact us to co‑develop assays, trials, and translational pipelines.