Prostate cancer research at the Centre exemplifies the dynamic interplay of laboratory-based discovery and patient-centred clinical application. Two transformative studies underscore this iterative translation:

1. Targeting myeloid chemotaxis to reverse prostate cancer therapy resistance: Published in Nature (Guo et al.), this study explores a paradigm shift in advanced prostate cancer treatment by disrupting the tumour ecosystems. Combining antiandrogen with CXCR2 inhibition re-sensitised resistant cancers, marking a significant advancement in targeting tumour microenvironments.

2. Elucidating acquired PARP inhibitor resistance in advanced prostate cancer: Published in Cancer Cell (Seed et al.), t his research identifies the emergence of PARP inhibitor resistance mechanisms in advanced prostate cancer. By leveraging serial circulating tumour DNA analyses, the study revealed that reversion mutations restoring homologous recombination repair drive resistance, highlighting a critical need for tailored therapeutic strategies.

Both cases underscore how discovery research, originating in molecular and cellular biology, translates rapidly into rapid "proof-of-concept" clinical trials, then cycles back to refine the understanding of underlying mechanisms.

The Convergence Science Centre has been instrumental, providing state-of-the-art facilities, funding for translational scientists, and the development of advanced methodologies such as single-cell DNA analysis and bioinformatic processing. These resources foster a robust ecosystem that bridges lab and clinic, enabling iterative progress.

Cancer evolution and the role of the epigenome in cancer - Mathematical sciences are increasingly transforming cancer research. The complexity and dynamic nature of cancer challenge traditional biology, requiring innovative approaches. Mathematical models reveal that cancer evolution within its microenvironment follows principles akin to Darwinian selection. At the Centre, researchers have shown that cancer progression is shaped not only by genetics but also by epigenetics, such as DNA modifications, and the regulation of mRNA and protein expression. Teams at ICR and Imperial have mapped epigenetic events driving colorectal cancer plasticity, with findings published in Nature (Heide et al., 2022; Househam et al. 2022). In prostate cancer, our researchers have mapped the evolution of tumours to predict cancer recurrence (Fernandez-Mateos et al. Nature Cancer, 2024). Similarly, in hormone-dependent breast cancer, Centre-supported studies published in Cancer Discovery  uncovered how epigenetics enables cancer cells to remain dormant for decades before re-emerging as treatment-resistant  (Barozzi et al.; Rosano et al., 2024). This work also offers strategies to target dormant cells before they reawaken.

Alan Turing and the Enigma of Pancreatic Cancer Heterogeneity - In a pioneering study published in Nature and led by Prof Axel Behrens, our Scientific Director, we made remarkable progress in understanding the aggressiveness of pancreatic cancer (Lan et al. 2022). A vital part of this breakthrough involved the 70-year-old equation of British polymath Alan Turing, demonstrating the far-reaching influence of his work in our discoveries. Pancreatic ductal adenocarcinoma (PDAC) is characterised by its varied cancer cell populations. Grasping this cellular heterogeneity is essential for discerning different disease subtypes and designing bespoke treatments. Our research has identified the BMP inhibitor GREM1 as a critical regulator of cellular diversity in pancreatic cancer, observed in both human patients and mouse models. This study lays the groundwork for developing smarter treatments to inhibit pancreatic tumour growth and metastasis.

Mathematical oncology and cancer evolution are proving vital in outsmarting cancer’s adaptability, providing innovative paths to drive it toward eradication.