Novel Drugs Targeting the Epidermal Growth Factor Receptor and Its Downstream Pathways in the Treatment of Colorectal Cancer: A Systematic Review

Abstract

Colorectal cancer is the second most common malignancy among men and women in the United States, and the 5-year survival rate remains poor despite recent advances in chemotherapy and targeted agents. The mainstay of therapy for advanced disease remains the cytotoxic chemotherapy including 5-FU, irinotecan, and oxaliplatin. The USFDA approval and introduction of targeted therapies, including cetuximab and panitumumab (monoclonal antibodies targeting the epidermal growth factor receptor (EGFR)) and bevacizumab (monoclonal antibody targeting the vascular epithelial growth factor (VEGF)), has improved the median survival of patients with metastatic colorectal cancer to around 24 months. Clearly, better and more efficacious drugs are needed, and target-specific agents remain the future of cancer treatment. On this front, rapid advances are being made, which are likely to change the future of the management of metastatic colorectal cancer. However, absence of specific biomarkers for the use of targeted agents, in the subset of population who will benefit from the treatment, remains a major drawback. In this paper, we review agents that are in phases 1 and 2 clinical development, specifically targeting the EGFR and its subsequent downstream pathways.

Layered Signaling Regulatory Networks Analysis of Gene Expression Involved in Malignant Tumorigenesis of Non-Resolving Ulcerative Colitis via Integration of Cross-Study Microarray Profiles

“…In the presence of EGFR, the accumulation of EGF in solid tumor led to the activation of the PI3K/AKT pathway which subsequently gave rise to solid tumor proliferation. Therefore, tactics targeting EGF/EGFR cascade system would have been an effective and timely approach for clinical prevention and therapeutic intervention for the transition from chronic non-resolving UC to pernicious colorectal carcinoma [80].…”

Current Status and Perspectives Regarding LNA‐Anti‐miR Oligonucleotides and microRNA miR‐21 Inhibitors as a Potential Therapeutic Option in Treatment of Colorectal Cancer

“…MEK 62/ARRY‐438162 is the best potential inhibitor for­ MEK1/MEK2 . It is already in phases 1 and 2 trials for many advanced solid tumors with mutations in KRAS, NRAS , and BRAF [Merla and Goel, ].…”

Understanding convergent signaling regulation in metastatic breast cancer cells using a bioengineered stem cell microenvironment

“…This causes a conformational change which exposes the activation loop and allows for protein binding and phosphorylation of downstream signaling targets [11,12] . Phosphorylation initiates signaling cascades, such as Ras/Raf/mitogen-activated protein kinase/ ERK, phosphoinositol 3 (PI3)-Akt-mechanistic target of rapamycin (mTOR), PLC-γ, JAK/signal transducers and activators of transcription (STAT), and Src kinase pathways [11][12][13] . These signaling pathways affect cell growth and proliferation, differentiation, invasion, migration, apoptosis, angiogenesis, cell cycle progression, and immune function [11,14,15] .…”