National Cancer Centre Singapore

The global cancer burden is rapidly rising, with current approximations of lifetime cancer development risk at least in one out of five individuals. Recent data suggest that the Asian region contributes the majority of the world’s incidence of cancer, with mortality rates estimated at over 4 million in 2020 (International Agency for Research on Cancer), highlighting a burgeoning need for improved diagnostics and novel therapeutic strategies to combat this problem. Simultaneously, we are witnessing an accelerated phase in knowledge acquisition through scientific research, rapidly expanding our understanding of the molecular pathophysiology of cancers from the global ethnogeography perspective. Asian-prevalent cancers have not only been associated with genetic variants distinctive to specific countries and regions, but have also been attributed to environmental risk factors including unique dietary practices, endemic pathogen exposures, and diverse lifestyle practices. In the context of Molecular Diagnostics, this implies a molecular diversity that needs to be carefully apprised by various stakeholders in order not to miss opportunities for biomarker discovery. Broad genomic information comprising single nucleotide variations, insertions, deletions, gene fusions, microsatellite instability, and tumor mutational burden have been incorporated into the oncology clinic through commercially available assays such as FoundationOne CDx (Foundation Medicine). More recently, an Asian Pan-Cancer Assay (Tissue500, Lucence) specifically designed using Asian-centric cancer biomarkers has also been launched to serve the needs of the Asian cancer patient community, further bridging the gulf between the oncologist and the ability to implement molecularly-informed precision treatment in the clinic. 

Assays using complex ex vivo models such as organoids and humanized mouse models may further enable temporal information to be integrated into a multi-dimensional “pan-omic” diagnostic assay of the future, driving forward a new era for precision oncology

 What is precision oncology? Simply put, it is about delivering to right cancer, the right therapy, at the right time - an ideal standard of care. But are the contemporary diagnostic tools we possess today the epitome of precision oncology? Not. The next generation of cancer diagnostic assays in development are already encompassing additional layers of molecular information, such as the tumor DNA methylome, chromatin modification landscape, metagenome, and proteome. Moreover, with the field of immuno-oncology progressing at a blistering pace, elements including the host microbiome, as well as systemic immune response, and other circulating analytes add further layers of complexity. It does not stop here - emerging platforms for single-cell sequencing and spatial “omic” technologies offer the ability to overcome issues of tissue heterogeneity at high resolution, and we are already moving on to potentially incorporate information at the subcellular level and perhaps someday even at the sub-molecular or atomic scale. Assays using complex ex vivo models such as organoids and humanized mouse models may further enable temporal information to be integrated into a multi-dimensional “pan-omic” diagnostic assay of the future, driving forward a new era for precision oncology.