Metastatic Colorectal Cancer: A Systematic Review of Disease Manifestation and Response to Treatment in Right- vs Left-Sided Adenocarcinoma

Abstract

Metastatic colorectal cancer (mCRC) is a well-known and recognized disease. It is a heterogeneous, progressive, non-cutaneous, multi-stage example of hyperactive cellular dysfunction and genetic overexpression. It is widely documented as being the third most prolific form of cellular carcinogenesis and it accounts for approximately 90% of malignancy in tumors within the large bowel. In recent years, advances in clinical research have revealed that much of the diversity associated with the manifestation of colonic adenoma may be linked to the heterogeneous embryonic origins of the colonic landscape. For example, adenocarcinoma of the proximal (ascending) right-side of the colon, which develops embryologically from the midgut, typically presents with microsatellite instability and a higher frequency of BRAF mutations. In contrast, disease expression within the distal (descending) left-side of the colon, which shares nascent origins with the hindgut, is characterized by chromosomal instability and activation of the epidermal growth factor receptor (EGFR) pathway. As a result, these variances highlight an important relationship between site-specific embryology and disease etiology. It is believed that a heterogeneous approach to therapeutic treatment methodologies based upon the biogeography of the colonic landscape, may hold an important key to unlocking and advancing the overall efficacy of first-line therapies used in the treatment of metastatic colorectal cancer. SPECIFIC AIMS: The purpose of this project is to perform a systematic review of primary literature from studies where-in targeted anti-VEGF and anti-EGFR treatments were administered as first-line therapy to patient populations inclusive of right-sided and/or left-sided colorectal cancer in order to evaluate the efficacy of site-specific treatment on Overall Survival (OS), Objective Response (OR), and Progression-Free Survival (PFS) rates.