Colorectal Cancer

Two pathways for the progression of colorectal cancer have been identified: chromosomal instability (CIN) and microsatellite instability (MIN or MSI).  About 85% of colorectal cancers are due to CIN and the remaining 15% arise from MIN. 

In the CIN pathway, the morphological change at each stage is often associated with alteration of specific genes.  Initially, a polyp forms on the colon wall, which is associated with loss of the APC tumor suppressor gene. Then, the progression from the polyp into a class II adenoma is accompanied by the activation of K-Ras. Subsequently, the loss of the DCC tumor suppressor gene converts the class II adenoma into class III adenoma. Finally, a carcinoma is developed by the loss of p53  (illustration from Lodish et al.).

The MIN pathway is characterized by defects in the DNA repair genes such as MLH1, MSH2, and MSH6  (reference).

Review Articles:

EphB/EphrinB Receptors and Wnt Signaling in Colorectal Cancer - Cancer Research, 2006.

An update on the genetics of colorectal cancer - Hum. Mol. Genetics, 2004.

Prostaglandin EP receptors: Targets for treatment and prevention of colorectal cancer? - Mol. Cancer Thera., 2004.

Pre-cancerous lesions for colorectal cancers in rodents: a new concept - Carcinogenesis, 2003.

b-Catenin---A Linchpin in Colorectal Carcinogenesis - Am. J. Pathol., 2002.

Where is APC going? - J. Cell Biology, 2001.

The Selection for Mismatch Repair Defects in Hereditary Nonpolyposis Colorectal Cancer - Cancer Research, 2001.