Chemoprophylaxis of precancerous lesions in patients who are at a high risk of developing colorectal cancer (Review)

Abstract

The diagnostics of colorectal cancer (CRC) and precancerous lesions in the colon is one of the most urgent matters to be considered for the modern protocols of complex examination, recommended for use from the age of 45 years, and including both instrumental and laboratory methods of research: Colonoscopy, CT colonography, flexible sigmoidoscopy, fecal occult blood test, fecal immunohistochemistry test and stool DNA test Nevertheless, the removal of those precancerous lesions does not solve the issue, and, apart from the regular endoscopic monitoring of patients who are at a high risk of developing CRC, the pharmacological treatment of certain key pathogenic mechanisms leading to the development of CRC is required. The present review to discusses the function of β-catenin in the transformation of precancerous colorectal lesions into CRC, when collaborating with PI3K/AKT/mTOR signaling pathway and other mechanisms. The existing methods for the early diagnostics and prevention of discovered anomalies are described and categorized. The analysis of the approaches to chemoprophylaxis of CRC, depending on the results of endoscopic, morphological and molecular-genetic tests, is presented.

Keywords: biological therapy; cancer stem cells; colorectal cancer; inflammatory bowel disease.

Figure 1

(A) A hyperplastic polyp, represented by a neoplasm with a serrated histoarchitecture, which develops as a result of impaired proliferation of the epithelium of the base of the crypts, which leads to the migration of proliferating cells into the apical parts of the intestinal crypts and the development of a serrated pattern. The tissue was obtained from a female patient, 70 years of age. The excision of the colon tumor was performed on May 22, 2023. A section of the mucous membrane of the colon measuring ~5.0 mm was prepared with further standard histological examination of the biopsy specimen and embedding in paraffin. Cutting was carried out using a microtome, with a section thickness of 4 µm. Standard hematoxylin and eosin staining was then performed. The magnification of the microscope cannot be reliably determined, since a series of images were taken with a magnification of x10 and subsequent stitching of the microphotographs. (B) Sissle serrated adenoma, represented by a neoplasm with basal localization of proliferation zones in the intestinal crypts and horizontal displacement of the proliferative zone, as well as the presence of dysplasia. The tissue was obtained from a female patient, 52 years of age. The excision of the colon tumor was performed on February 27, 2023. A flat section of the colon mucosa with a diameter of ~1.7 mm, with serial sections was prepared, with further standard histological processing of the biopsy specimen, and embedding in paraffin. Cutting was carried out using a microtome, with a section thickness of 4 µm. Standard hematoxylin and eosin staining was then performed. The magnification of the microscope cannot be reliably determined, since a series of images were taken with a magnification of x10 and subsequent stitching of the microphotographs. (C) Tubular adenoma, represented by a neoplasm with the presence of a classic tubular pattern with dysplastic changes, elongation, an increase in the number of tubules and the development of finger-like outgrowths. The tissue was obtained from a female patient, 49 years of age. The excision of the colon tumor was performed on June 1, 2023. The image depicts an exophytic neoplasm of the colon mucosa, pedunculated, 1.4 and 1.0 cm in size, with serial sections; further standard histological examination of the biopsy specimen and embedding in paraffin were performed. The section was cut was carried using a microtome, with a section thickness of 4 µm. Standard hematoxylin and eosin staining was performed. The magnification of the microscope cannot be reliably determined, since a series of images were taken with a magnification of x10 and subsequent stitching of the microphotographs. (D) Dysplasia in inflammatory bowel disease is characterized by a peculiar arrangement of dysplastic epithelial cells occupying the entire crypt. The tissue was obtained from a male patient, 66 years of age, with an established diagnosis of inflammatory bowel disease, namely ulcerative colitis. A colon biopsy was performed on November 30, 2022. A biopsy of the colon mucosa, 0.5 mm in size, with further standard histological examination of the biopsy and embedding in paraffin were performed. Cutting was then carried out using a microtome, with a section thickness of 4 µm. Standard hematoxylin and eosin staining was performed. The image is presented as x10 magnification with stitching of the microphotographs.

Figure 2

Pathogenesis of β-catenin accumulation in the canonical and non-canonical WNT signaling pathway, as well as alternative mechanisms of nuclear β-catenin accumulation in the nucleus with a predominant effect on GSK-3β. GSK-3, glycogen synthase kinase-3; TCF/LEF, T-cell factor/lymphoid enhancer factor; AXIN 1/2, AXIS inhibition protein; CK1, casein kinase 1; APС; PI3K, phosphatidylinositol-3-kinase; AKT, protein kinase B; mTOR, mammalian target of rapamycin; DVL, Dishevelled; LRP5/6, low-density lipoprotein receptor-related protein.

Figure 3

Pathogenesis of the development of cryptitis and crypt abscess. ROS, reactive oxygen species; MMP, matrix metalloproteinase.