Colorectal Cancers: An Update on Their Molecular Pathology

Abstract

Colorectal cancers (CRCs) are the third leading cause of cancer-related mortality worldwide. Rather than being a single, uniform disease type, accumulating evidence suggests that CRCs comprise a group of molecularly heterogeneous diseases that are characterized by a range of genomic and epigenomic alterations. This heterogeneity slows the development of molecular-targeted therapy as a form of precision medicine. Recent data regarding comprehensive molecular characterizations and molecular pathological examinations of CRCs have increased our understanding of the genomic and epigenomic landscapes of CRCs, which has enabled CRCs to be reclassified into biologically and clinically meaningful subtypes. The increased knowledge of the molecular pathological epidemiology of CRCs has permitted their evolution from a vaguely understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes, a development that will allow the implementation of personalized therapies and better management of patients with CRC. This review provides a perspective regarding recent developments in our knowledge of the molecular and epidemiological landscapes of CRCs, including results of comprehensive molecular characterizations obtained from high-throughput analyses and the latest developments regarding their molecular pathologies, immunological biomarkers, and associated gut microbiome. Advances in our understanding of potential personalized therapies for molecularly specific subtypes are also reviewed.

CTHRC1 overexpression predicts poor survival and enhances epithelial‐mesenchymal transition in colorectal cancer

“…EMT progression involves the localized occurrence of a loss of epithelial differentiation and the acquisition of a mesenchymal phenotype. This process enhances the motility and invasion of cancer cells and plays an important part in the consensus molecular subtype (CMS) classifications . CRCs with EMT signature are classified into CMS4 subgroup (an EMT‐related subtype), characterized as more aggressive phenotype showing poorer overall survival and signatures of high TGF‐β signaling and EMT activation .…”

Evaluation of p53 expression among Colorectal Cancer patients

“…Besides , among cancer-related mortality, the third most common cause of death was due to the CRC (Inamura, 2018). According to the statics of 2008, the estimation regarding the incidence and mortality of CRC showed that, approximately 50,000 death among the whole of 150,000 diagnosed cases (László, 2010).…”

Loss of expression of μ-protocadherin and protocadherin-24 in sporadic and hereditary nonpolyposis colorectal cancers

“…Colorectal cancer (CRC) is a neoplastic condition of great medical and social interest, and despite the considerable progress achieved in the comprehension of its molecular pathogenesis, it remains the most frequent tumor in general population and the second cause of cancer-related death in Western countries [1]. The development of CRC is a multistep process in which a series of genetic and epigenetic alterations activates proto-oncogenes and inactivates oncosuppressor genes, leading to the malignant transformation of colorectal mucosa cells [2,3]. The initial, and probably most important, among such modifications determines a constitutive activation of the βcatenin signaling pathway, resulting in an increased proliferation of CRC cells.…”