Genetic and epigenetic dependencies in colorectal cancer development

Abstract

Recent studies have mapped key genetic changes in colorectal cancer (CRC) that impact important pathways contributing to the multistep models for CRC initiation and development. In parallel with genetic changes, normal and cancer tissues harbor epigenetic alterations impacting regulation of critical genes that have been shown to play profound roles in the tumor initiation. Cumulatively, these molecular changes are only loosely associated with heterogenous transcriptional programs, reflecting the heterogeneity in the various CRC molecular subtypes and the paths to CRC development. Studies from mapping molecular alterations in early CRC lesions and use of experimental models suggest that the intricate dependencies of various genetic and epigenetic hits shape the early development of CRC via different pathways and its manifestation into various CRC subtypes. We highlight the dependency of epigenetic and genetic changes in driving CRC development and discuss factors affecting epigenetic alterations over time and, by extension, risk for cancer.

Analysis of the relationship between the gut microbiota enterotypes and colorectal adenoma

“…Colorectal cancer is one of the third most common types of cancer in the world and it is also the main cause of cancer death ( Cao et al, 2021 ; Sung et al, 2021 ; Xie et al, 2021 ). Colorectal cancer is a complex disease influenced by genetics, diet, chronic inflammation, and environmental factors ( Dekker et al, 2019 ; Nguyen et al, 2020 ; Parmar and Easwaran, 2022 ). Moreover, advanced polyps are closely related to the occurrence of colorectal cancer ( Leslie et al, 2002 ; He et al, 2018 ).…”

Epigenetic Rewiring of Metastatic Cancer to the Brain: Focus on Lung and Colon Cancers

“…Hypermethylation in CRC, also known as the CpG island methylator phenotype (CIMP), has already been described in primary tumors [ 28 ] and the CRC epigenome has been demonstrated to facilitate the accumulation of genomic mutations in cancer key genes [ 29 ]. The CIMP-high CRC phenotype has been associated with poor prognosis and cancer aggressiveness [ 30 ]. Our data confirm this notion providing that brain metastasis from CRC maintains the hypermethylated status observed in primary tumors and shows modest hypomethylation at metastasis-specific regions, i.e., promoters of genes involved in metabolic pathways.…”

Metabolic reprogramming in colorectal cancer: regulatory networks and therapy

“…The results of clinical trials performed to evaluate promising IDO1 inhibitors have been disappointing, which highlights the need for a deeper understanding of the precise effector mechanisms of tumor metabolism in vivo [131]. Additionally, only 13% of CRC cases have been characterized by metabolic reprogramming (CMS3) [224,225]. Enzymes involved in metabolic reprogramming are altered to fuel CRC carcinogenesis and resistance to stress.…”