LUMES LUng cancer Metastasis Evolutionary Studies

Metastatic disease, describing the development of secondary malignant growths at a distance from a primary site of cancer, is associated with over 90% of cancer-related deaths. There exists a significant unmet clinical need to better understand the biology of aggressive cancers leading to metastatic disease and the underlying mechanisms that can facilitate the metastasis. Previous studies exploring metastasis have suffered from scarcity of samples, insufficient resolution and breadth of experimental data, and a lack of appropriate computational and statistical tools. These inadequacies have led to significant ambiguities in data interpretation resulting in a substantial knowledge gap, hindering translational opportunities to tackle metastatic disease. LUMES will provide crucial contributions towards an in-depth understanding of metastasis by (1) exploiting access to the singular Posthumous Evaluation of Advanced Cancer Environment (PEACE; NCT03004755) research autopsy programme with extensive sampling from both primary and metastatic sites to generate a unique resource for exploration of metastatic cancer evolution, (2) applying cutting-edge experimental techniques to human samples, (3) developing advanced novel AI enhanced computational and statistical tools designed to study metastasis and metastatic spread, (4) applying an integrative view of cancer development, incorporating genetic and non-genetic analysis of cancer-cell intrinsic and extrinsic features as well as ctDNA, in the context of the tumour microenvironment and detailed clinical annotation, including exposure to cancer therapies. Importantly, (1) and (2) provide an indispensable fundament for (3) and (4). The synergies between (3) and (4) are immense. Computational method development and application should be coupled. Our work will enable a deep understanding of the metastatic process and reveal key differences in cancer cell intrinsic and microenvironment between distinct patterns of metastasis.