#IDIBELLseminars: Brain Tumours: Understanding Biology, Advancing Early Detection

Glioblastoma (GBM) remains one of the most lethal solid tumours, defined by profound molecular heterogeneity, intrinsic therapeutic resistance, and near universal recurrence. Across my career, my research has centred on understanding the molecular drivers of glioma progression and treatment failure, spanning angiogenic signalling, aberrant DNA repair, cancer stem cell biology, and development of clinically relevant pre clinical models. These efforts have revealed mechanisms of bevacizumab escape, identified vulnerabilities in DNA damage response and replication stress pathways, and contributed to the development of brain penetrant therapeutics including PARP1 and ATM inhibitors now in clinical investigation.
More recently, my group has focused on advancing non invasive diagnostics to address long standing challenges in early detection and real time monitoring of GBM. In our latest study, we performed integrated proteomic profiling of paired tumour and plasma samples, demonstrating that despite extensive tumour intrinsic heterogeneity, plasma proteomes are strikingly homogeneous across patients and disease stages. From these systemic signatures, we developed a robust dual marker plasma classifier, which distinguishes GBM patients from healthy individuals with high accuracy and captures dynamic treatment associated changes. These findings support the feasibility of a simple blood based assay capable of detecting GBM and monitoring its evolution, with the potential to complement imaging and reduce reliance on invasive tissue sampling.
Together, our work underscores the value of integrating mechanistic tumour biology with translational biomarker discovery. I will discuss how these insights pave the way for precision guided therapeutic strategies and next generation liquid biopsy approaches for adult and paediatric brain tumours.

Hosted by Barbara Rivera – Hereditary cancer group

Professor Petra Hamerlik is Chair of Translational Neuro‑Oncology at the University of Manchester and a leading researcher in the biology, treatment resistance, and early detection of brain tumours. Her work investigates why aggressive cancers such as glioblastoma are so difficult to treat, uncovering mechanisms including replication stress, DNA damage response activation, and adaptive VEGF–VEGFR2 signalling that allow these tumours to evade therapy. These insights informed her translational work in industry, where at AstraZeneca she contributed to the development of new brain‑penetrant cancer medicines, including the PARP1 inhibitor AZD9574 and the ATM inhibitor AZD1390, now in clinical testing. Alongside mechanistic research, Professor Hamerlik’s laboratory develops advanced patient‑derived tumour models and leads innovation in liquid biopsies—using small, non‑invasive samples such as blood and tear fluid to detect molecular changes linked to brain cancer. She leads INFORM, a prospective NHS REC‑approved multi‑centre study developing early detection and monitoring assays for gliomas, paediatric brain tumours and brain metastases. Her seminar will show how fundamental biology, state‑of‑the‑art preclinical models, and next‑generation liquid biopsy technologies are coming together to transform early diagnosis and personalised monitoring for people with brain tumours.