Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells

Abstract

Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20–30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse.

RETRACTED ARTICLE: Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway

“…There is a wide range of heterogeneity between colon cancer types, with nearly 30% of cases stemming from hereditary mutations and the remainder arising from de novo acquired mutations [5,6]. This heterogeneity can lead to the development of colon cancer via a number of pathways whereby adenocarcinomas develop from increasingly mutated gastrointestinal epithelial cells through the mutation of different oncogenes or tumor suppressor genes, resulting in differing levels of sensitivity to specific chemotherapeutic agents depending on the particular mutations driving a given case of the disease [7][8][9].…”

Disparate cell proliferation and p53 overexpression in colonic crypts with normal epithelial lining found below the neoplastic canopy of conventional adenomas

“…Using ×10 ocular lenses and a ×2 Plan Apo objective (FOV = 10 mm) showed that 12 of the 70 CoAs measured ≤10 mm (mean 8.4 mm, range 7-10 mm), and the remaining 58 CoAs measured >11 mm (mean 16.1 mm, range 12-23 mm). The number of NECS in the 12 small CoA was 184 (mean 19.3, range 6-30), and the number of NECS in 14 unselected large CoAs was 267 (mean 20.1, range [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. The differences in the frequency of NECS between small and large CoAs was nonsignificant (p = 0.12).…”

The perils of toxic masculinity: four case studies

“…9 Although some cases of colon cancer are familial, it has been estimated that about half of colorectal cancer cases are the result of lifestyle factors, and about a quarter of all cases are preventable. 10 Namely, if overweight or obese, the risk of developing and dying from colorectal cancer is higher. Being overweight (especially having a larger waistline) raises the risk of colon and rectal cancer in both men and women.…”