Molecular Genetics and the Role of Molecularly Targeted Agents in Metastatic Colorectal Carcinoma

Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. It is the third most common malignancy and fourth leading cancer-related deaths worldwide. In the USA, CRC is the third most commonly diagnosed cancer in both men and women. It is caused by genetic components and potential environmental factors such as consumption of processed meat, red meat, animal fats, low fiber intake, and obesity. Despite the utilization of effective screening modalities and guidelines in the USA, a significant number of patients are diagnosed with advanced, metastatic disease at the time of presentation to the physician. Recent advances in the understanding of molecular medicine with subsequent development and incorporation of newer therapeutic agents into current chemotherapeutic regimens have improved outcomes; however, the management of metastatic CRC remains challenging, particularly for the treating oncologists.

We conducted a literature search on CRC mainly related to molecular genetics, targeted biologic agents, and published clinical trials. We also searched and reviewed ongoing clinical trials from Clinicaltrials.gov.

Alterations in several oncogenes are associated with CRC, among those RAS, BRAF, and HER2 are of current clinical importance. Chemotherapy drugs, along with vascular endothelial growth factor or epidermal growth factor receptor monoclonal antibodies, are proven to be efficient with manageable toxicity profiles in metastatic CRC. Additional researches on Her-2-directed therapy, BRAF-targeted agents, immunotherapeutic, and newer molecularly targeted agents are needed for further improvement in outcome.