The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy

Abstract

Colorectal cancer (CRC) results from the progressive accumulation of multiple genetic and epigenetic aberrations within cells. The progression from colorectal adenoma to carcinoma is caused by three major pathways: Microsatellite instability, chromosomal instability and CpG island methylator phenotype. A growing body of scientific evidences suggests that CRC is a heterogeneous disease, and genetic characteristics of the tumors determine their prognostic outcome and response to targeted therapies. Early diagnosis and effective targeted therapies based on a current knowledge of the molecular characteristics of CRC are essential to the successful treatment of CRC. Therefore, the present review summarized the current understanding of the molecular characteristics of CRC, and discussed its implications for diagnosis and targeted therapy.

Keywords: CpG island methylator phenotype; chromosomal instability; colorectal cancer; early diagnosis; microsatellite instability; molecular characteristics; targeted therapy.

Figure 1.

Colorectal adenoma-carcinoma sequence. The APC mutation is the first step transforming normal colorectal epithelium to adenoma. The adenoma-carcinoma sequence is caused by three major pathways: CIN, MSI and CIMP. CIN, Chromosomal instability; MSI, microsatellite instability; CIMP, CpG island methylator phenotype; APC, adenomatous polyposis; KRAS, KRAS proto-oncogene GTPase; BRAF, B-Raf proto-oncogene serine/threonine kinase; TP53, tumor protein 53; LOH, loss of heterozygosity; HNPPC, hereditary non-polyposis colorectal cancer; MLH1, mutL homolog 1; MSH2, mutS homolog 2; DCC, DCC netrin 1 receptor; TGFBR, transforming growth factor-β receptor; BAX, BCL2 associated X apoptosis regulator; IGF2R, insulin like growth factor 2 receptor; CDC4, cell division control protein 4.

Figure 2.

Overview of the genetic and epigenetic instability pathways that drive colorectal cancer onset and development. CIN, Chromosomal instability; MSI, microsatellite instability; CIMP, CpG island methylator phenotype; APC, adenomatous polyposis; KRAS, KRAS proto-oncogene GTPase; BRAF, B-Raf proto-oncogene serine/threonine kinase; TP53, tumor protein 53; LOH, loss of heterozygosity; HNPPC, hereditary non-polyposis colorectal cancer; MLH1, mutL homolog 1; MSH2, mutS homolog 2.