Current Targeted Therapy for Metastatic Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer deaths worldwide. Surgery or surgery plus radiotherapy and/or chemotherapy for patients with metastatic CRC (mCRC) were accepted as the main therapeutic strategies until the early 2000s, when targeted drugs, like cetuximab and bevacizumab, were developed. The use of targeted drugs in clinical practice has significantly increased patients' overall survival. To date, the emergence of several types of targeted drugs has opened new possibilities and revealed new prospects for mCRC treatment. Therapeutic strategies are continually being updated to select the most suitable targeted drugs based on the results of clinical trials that are currently underway. This review discusses the up-to date molecular evidence of targeted therapy for mCRC and summarizes the Food and Drug Administration-approved targeted drugs including the results of clinical trials. We also explain their mechanisms of action and how these affect the choice of a suitable targeted therapy.

Keywords: clinical trial; colorectal cancer; targeted therapy.

Figure 1

Comprehensive overview of FDA-approved targeted drugs for mCRC. Abbreviations: EGFR: epidermal growth factor receptor; FGFR: fibroblast growth factor receptor; VEGFR: vascular endothelia growth factor receptor; TRK: tropomyosin receptor kinase; VEGF: vascular endothelial growth factor; PlGF: placenta growth factor; PD-1: programmed cell death 1; PD-L1: programmed cell death ligand 1; CTLA-4: cytotoxic T-lymphocyte-associated protein-4; B7: CD80/CD86; MEK: mitogen-activated protein kinase; ERK: extracellular signal-regulated kinase; PI3K: phosphoinositide 3-kinase; mTOR: mechanistic target of rapamycin; PLC-γ: phospholipase C-γ; PKC: protein kinase C; NF-kB: nuclear factor-kappa B; JAK: Janus kinase; STAT: transducer and activator of transcription.