Metabolomics and the Multi-Omics View of Cancer

Abstract

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.

Research Progress of RNA Methylation Modification in Colorectal Cancer

“…Epigenetic modifications are dynamically reversible and heritable, including DNA methylation, histone modifications, chromatin remodeling, microRNAs (miRNAs) and noncoding RNAs (ncRNAs) which are of great importance in the progression and metastasis of colorectal cancer ( Huang et al, 2021a ). Recently, major breakthroughs have been made in the research on DNA omics and proteomics in the occurrence and development of tumors, and the epigenetic modification at the RNA level has also attracted the attention of many researchers ( Skvortsova et al, 2019 ; Sivanand and Vander Heiden, 2020 ; Mobet et al, 2022 ; Wishart, 2022 ).…”

Pathways to Identify Electrophiles In Vivo Using Hemoglobin Adducts: Hydroxypropanoic Acid Valine Adduct and Its Possible Precursors

“…Increasing evidence supports that environmental exposures are major contributors to the development of cancer and other chronic diseases. − The importance of environmental factors in cancer etiology was highlighted already in the 1970s by J. Higginson, who considered the environment in a broad view, including lifestyle factors, as diet and cultural habits, as well as chemical exposure. , In 2005, the concept of the exposome was proposed by C. Wild and described as the “life-course environmental exposures (including lifestyle factors), from the prenatal period onwards”, which was later redefined to include exposure from endogenous processes . The concept was introduced to emphasize the significance of environmental exposures as contributors of common chronic diseases, to balance the focus placed on the genome, and to highlight the need for more holistic methods for exposure assessment.…”

Hematogenous metastasis and tumor dormancy as concepts or dogma? The continuum of vessel co-option and angiotropic extravascular migratory metastasis as an alternative

“…By the beginning of the 21 st century, with the increasing significance of developmental biology, some researchers questioned the reductionism in molecular biology ( 12 ). In contrast, as shown by an ever-increasing number of publications, the genomic perspective virtually controls the field of biomedical research ( 13 ). With the first publication of the sequencing of the human genome, many researchers aggressively embraced the reductionist agenda that gave rise to precision medicine (Genome International Sequencing Consortium 2001) ( 12 , 14 ).…”