Immunotherapies and Targeted Therapies in the Treatment of Metastatic Colorectal Cancer
Colorectal cancer (CRC) is the third leading cause of cancer deaths, and while mortality has largely improved in the developed world, five-year survival for metastatic disease remains dismally low at only 15%. Fortunately, nearly a dozen targeted therapies and immunotherapies have been FDA approved...
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doaj-b9349a3bea2a4b409d95fd7df9073db02020-11-25T01:23:28ZengMDPI AGMedical Sciences2076-32712019-07-01788310.3390/medsci7080083medsci7080083Immunotherapies and Targeted Therapies in the Treatment of Metastatic Colorectal CancerPrashanth Rawla0Adam Barsouk1Andreas V. Hadjinicolaou2Alexander Barsouk3Department of Medicine, Sovah Health, Martinsville, VA 24112, USAHillman Cancer Center, University of Pittsburgh, PA 15232, USAAcademic Clinical Post-doctoral Fellow and Gastroenterology Resident, MRC Cancer Unit and Department of Gastroenterology, University of Cambridge, Cambridge CB2 0XZ, UKHematologist-Oncologist, Allegheny Health Network, Pittsburgh, PA 15212, USAColorectal cancer (CRC) is the third leading cause of cancer deaths, and while mortality has largely improved in the developed world, five-year survival for metastatic disease remains dismally low at only 15%. Fortunately, nearly a dozen targeted therapies and immunotherapies have been FDA approved in the past decade for certain patient profiles with metastatic CRC (mCRC), and many others are under development. Checkpoint inhibitors such as pembrolizumab have proven effective at extending survival for mismatch repair (MMR)-deficient and high microsatellite instability (MSI) mCRC patients. In combination with chemotherapy in first- and second-line treatment, antiangiogenic (anti-vascular endothelial growth factor (anti-VGEF)) agent bevacizumab has been shown to increase mCRC survival. Anti-epidermal growth factor receptor (anti-EGFR) agents panitumumab and cetuximab, in combination with chemotherapy, have also prolonged survival among <i>KRAS</i> and all <i>RAS</i> wild-type mCRC patients. Among these patients, anti-EGFR therapy has been found to be more efficacious than bevacizumab. Improved selectivity has allowed small-molecule receptor tyrosine kinase (RTK) inhibitors to target VEGF and EGFR with greater efficacy and tolerability. Combinations of immunotherapies, RTKs, monoclonal antibodies, and cytotoxic drugs are being investigated to provide broad-spectrum protection against relapse by simultaneously targeting many cancer hallmarks. Lastly, human epidermal growth factor receptor 2 (HER2) therapy has shown promise for HER2-positive mCRC patients, though larger clinical trials are required to secure FDA approval.https://www.mdpi.com/2076-3271/7/8/83colorectalmetastatictargeted therapyepidermal growth factor receptor inhibitorsnovel therapeutics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Prashanth Rawla Adam Barsouk Andreas V. Hadjinicolaou Alexander Barsouk |
spellingShingle |
Prashanth Rawla Adam Barsouk Andreas V. Hadjinicolaou Alexander Barsouk Immunotherapies and Targeted Therapies in the Treatment of Metastatic Colorectal Cancer Medical Sciences colorectal metastatic targeted therapy epidermal growth factor receptor inhibitors novel therapeutics |
author_facet |
Prashanth Rawla Adam Barsouk Andreas V. Hadjinicolaou Alexander Barsouk |
author_sort |
Prashanth Rawla |
title |
Immunotherapies and Targeted Therapies in the Treatment of Metastatic Colorectal Cancer |
title_short |
Immunotherapies and Targeted Therapies in the Treatment of Metastatic Colorectal Cancer |
title_full |
Immunotherapies and Targeted Therapies in the Treatment of Metastatic Colorectal Cancer |
title_fullStr |
Immunotherapies and Targeted Therapies in the Treatment of Metastatic Colorectal Cancer |
title_full_unstemmed |
Immunotherapies and Targeted Therapies in the Treatment of Metastatic Colorectal Cancer |
title_sort |
immunotherapies and targeted therapies in the treatment of metastatic colorectal cancer |
publisher |
MDPI AG |
series |
Medical Sciences |
issn |
2076-3271 |
publishDate |
2019-07-01 |
description |
Colorectal cancer (CRC) is the third leading cause of cancer deaths, and while mortality has largely improved in the developed world, five-year survival for metastatic disease remains dismally low at only 15%. Fortunately, nearly a dozen targeted therapies and immunotherapies have been FDA approved in the past decade for certain patient profiles with metastatic CRC (mCRC), and many others are under development. Checkpoint inhibitors such as pembrolizumab have proven effective at extending survival for mismatch repair (MMR)-deficient and high microsatellite instability (MSI) mCRC patients. In combination with chemotherapy in first- and second-line treatment, antiangiogenic (anti-vascular endothelial growth factor (anti-VGEF)) agent bevacizumab has been shown to increase mCRC survival. Anti-epidermal growth factor receptor (anti-EGFR) agents panitumumab and cetuximab, in combination with chemotherapy, have also prolonged survival among <i>KRAS</i> and all <i>RAS</i> wild-type mCRC patients. Among these patients, anti-EGFR therapy has been found to be more efficacious than bevacizumab. Improved selectivity has allowed small-molecule receptor tyrosine kinase (RTK) inhibitors to target VEGF and EGFR with greater efficacy and tolerability. Combinations of immunotherapies, RTKs, monoclonal antibodies, and cytotoxic drugs are being investigated to provide broad-spectrum protection against relapse by simultaneously targeting many cancer hallmarks. Lastly, human epidermal growth factor receptor 2 (HER2) therapy has shown promise for HER2-positive mCRC patients, though larger clinical trials are required to secure FDA approval. |
topic |
colorectal metastatic targeted therapy epidermal growth factor receptor inhibitors novel therapeutics |
url |
https://www.mdpi.com/2076-3271/7/8/83 |
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