Cancer is widely regarded to be a genetic disease. Indeed, over the past five decades, the genomic perspective on cancer has come to almost completely dominate the field. However, this genome-only view is incomplete and tends to portray cancer as a disease that is highly heritable, driven by hundreds of complex genetic interactions and, consequently, difficult to prevent or treat. New evidence suggests that cancer is not as heritable or purely genetic as once thought and that it really is a multi-omics disease. As highlighted in this review, the genome, the exposome, and the metabolome all play roles in cancer's development and manifestation. The data presented here show that >90% of cancers are initiated by environmental exposures (the exposome) which lead to cancer-inducing genetic changes. The resulting genetic changes are, then, propagated through the altered DNA of the proliferating cancer cells (the genome). Finally, the dividing cancer cells are nourished and sustained by genetically reprogrammed, cancer-specific metabolism (the metabolome). As shown in this review, all three "omes" play roles in initiating cancer. Likewise, all three "omes" interact closely, often providing feedback to each other to sustain or enhance tumor development. Thanks to metabolomics, these multi-omics feedback loops are now much more evident and their roles in explaining the hallmarks of cancer are much better understood. Importantly, this more holistic, multi-omics view portrays cancer as a disease that is much more preventable, easier to understand, and potentially, far more treatable.
Keywords: cancer; exposome; genome; metabolome; metabolomics; metabotypes; oncometabolites.