Journal of Medical Council of Iran
مجله علمی پژوهشی سازمان نظام پزشکی
Volume 42, Issue 4 (2025)
jmciri 2025, 42(4): 38-51 |
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Alamdar M, Rezaei K, Akrami M. Comprehensive Examination of Targeted Therapies for Metastatic Colorectal Cancer: An Overview of Contemporary Approaches in Targeted Molecular Treatment and the Application of Tumor Biomarkers in Managing Metastatic Colorectal Cancer. jmciri 2025; 42 (4) :38-51
URL: http://jmciri.ir/article-1-3334-en.html
URL: http://jmciri.ir/article-1-3334-en.html
Professor, Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Abstract: (38 Views)
Abstract
Background: Colorectal cancer ranks as the third most prevalent cancer and stands as the second foremost cause of mortality globally. The median overall survival for individuals with previously untreated advanced colorectal cancer has improved to a range of 25 to 30 months, attributed to the integration of molecularly targeted therapies alongside chemotherapy. The main approach for managing unresectable metastatic colorectal cancer involves systemic therapy, which encompasses cytotoxic chemotherapy, biologic therapies like antibodies targeting cellular growth factors, immunotherapy, and various combinations of these modalities. Recent clinical trials conducted over the last five years have shown that customizing treatment based on the molecular and pathological characteristics of the tumor can enhance overall survival rates. The utilization of genomic profiling to identify somatic variants is crucial, as it helps pinpoint potentially effective treatment options.
Methods: This investigation examined the significance of targeted therapy in the treatment of patients with metastatic colorectal cancer, alongside an evaluation of emerging therapeutic strategies, through a comprehensive review of diverse literature pertaining to various approaches in the management of colorectal cancer.
Results: Treatment approaches for localized colorectal cancer predominantly involve surgical intervention and chemotherapy. In contrast, strategies for managing metastatic colorectal cancer are advancing, particularly through the identification of biomarkers that facilitate targeted therapies. These include inhibitors of the epidermal growth factor receptor (EGFR), serine/threonine-protein kinase B-Raf (BRAF), enhanced human epidermal growth factor receptor 2 (HER2), immune checkpoint inhibitors, and neurotrophic receptor tyrosine kinase (NTRK) inhibitors. Current predictive biomarkers for patients with metastatic colorectal cancer encompass mutations in RAS (rat sarcoma virus), BRAF mutations, microsatellite instability (MSI), mismatch repair deficiency (dMMR), HER2 amplifications, and NTRK fusions. The primary challenge lies in the effective integration of these advancements into routine clinical practice.
Conclusion: This review examines the contemporary predictive biomarkers relevant to patients with metastatic colorectal cancer and their corresponding targeted therapies. It highlights novel factors influencing anti-EGFR treatments, including the location of the primary tumor and the evaluation of immunosuppressants for microsatellite instability (MSI). Additionally, it addresses recent advancements in the treatment of BRAFV600E mutated cancers, as well as the roles of anti-HER2 therapies and NTRK inhibitors.
Background: Colorectal cancer ranks as the third most prevalent cancer and stands as the second foremost cause of mortality globally. The median overall survival for individuals with previously untreated advanced colorectal cancer has improved to a range of 25 to 30 months, attributed to the integration of molecularly targeted therapies alongside chemotherapy. The main approach for managing unresectable metastatic colorectal cancer involves systemic therapy, which encompasses cytotoxic chemotherapy, biologic therapies like antibodies targeting cellular growth factors, immunotherapy, and various combinations of these modalities. Recent clinical trials conducted over the last five years have shown that customizing treatment based on the molecular and pathological characteristics of the tumor can enhance overall survival rates. The utilization of genomic profiling to identify somatic variants is crucial, as it helps pinpoint potentially effective treatment options.
Methods: This investigation examined the significance of targeted therapy in the treatment of patients with metastatic colorectal cancer, alongside an evaluation of emerging therapeutic strategies, through a comprehensive review of diverse literature pertaining to various approaches in the management of colorectal cancer.
Results: Treatment approaches for localized colorectal cancer predominantly involve surgical intervention and chemotherapy. In contrast, strategies for managing metastatic colorectal cancer are advancing, particularly through the identification of biomarkers that facilitate targeted therapies. These include inhibitors of the epidermal growth factor receptor (EGFR), serine/threonine-protein kinase B-Raf (BRAF), enhanced human epidermal growth factor receptor 2 (HER2), immune checkpoint inhibitors, and neurotrophic receptor tyrosine kinase (NTRK) inhibitors. Current predictive biomarkers for patients with metastatic colorectal cancer encompass mutations in RAS (rat sarcoma virus), BRAF mutations, microsatellite instability (MSI), mismatch repair deficiency (dMMR), HER2 amplifications, and NTRK fusions. The primary challenge lies in the effective integration of these advancements into routine clinical practice.
Conclusion: This review examines the contemporary predictive biomarkers relevant to patients with metastatic colorectal cancer and their corresponding targeted therapies. It highlights novel factors influencing anti-EGFR treatments, including the location of the primary tumor and the evaluation of immunosuppressants for microsatellite instability (MSI). Additionally, it addresses recent advancements in the treatment of BRAFV600E mutated cancers, as well as the roles of anti-HER2 therapies and NTRK inhibitors.
Keywords: Colorectal cancer, immunotherapy, metastasis, molecular targeted therapy, tumor biomarkers.
Type of Study: Review |
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