Target Genetic Abnormalities for the Treatment of Colon Cancer and Its Progression to Metastasis

Curr Drug Targets. 2021;22(7):722-733. doi: 10.2174/1389450121666201119141015.

Abstract

Colorectal carcinogenesis involves various processes from the accumulation of genetic alterations to genetic and epigenetic modulations and chromosomal abnormalities. It also involves mutations in oncogenes and tumour suppressor genes. Genomic instability plays a vital role in CRC. Advances in modern biological techniques and molecular level studies have identified various genes involved in colorectal cancer (CRC). KRAS, BRAF, PI3K, and p53 genes play a significant role in different phases of CRC. Alteration of these genes leads to development or progression and metastasis colon cancer. This review focuses on the role of KRAS, BRAF, PI3KCA, and TP53 genes in carcinogenesis and their significance in various stages of CRC. It also provides insights on specific modulators acting on these genes. Further, this review discusses the mechanism of the pathways involving these genes in carcinogenesis and current molecules and treatment options under various stages of clinical evaluation.

Keywords: BRAF gene; Genetic alterations; KRAS gene; Metastatic colon cancer; P53 gene; PI3K gene.

Publication types

  • Review

MeSH terms

  • Carcinogenesis
  • Colonic Neoplasms* / drug therapy
  • Colonic Neoplasms* / genetics
  • Humans
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Transcription Factors / genetics
  • Tumor Suppressor Protein p53 / genetics

Substances

  • PI3KCA protein, human
  • TP53 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)