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Precision Medicine for Metastatic Colorectal Cancer: Where Do We Stand?
Patrick W Underwood1, Timothy M Pawlik1
1Department of Surgery, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH 43210, USA.
Abstract:
Metastatic colorectal cancer is a leading cause of cancer-related death across the world. The treatment paradigm has shifted away from systemic chemotherapy alone to include targeted therapy and immunotherapy. The past two decades have been characterized by increased investigation into molecular profiling of colorectal cancer. These molecular profiles help physicians to better understand colorectal cancer biology among patients with metastatic disease. Additionally, improved data on genetic pathways allow for specific therapies to be targeted at the underlying molecular profile. Investigation of the EGFR, VEGF, HER2, and other pathways, as well as deficient mismatch repair, has led to the development of multiple targeted therapies that are now utilized in the National Comprehensive Cancer Network guidelines for colon and rectal cancer. While these new therapies have contributed to improved survival for metastatic colorectal cancer, long-term survival remains poor. Additional investigation to understand resistance to targeted therapy and development of new targeted therapy is necessary. New therapies are under development and are being tested in the preclinical and clinical settings. The aim of this review is to provide a comprehensive evaluation of molecular profiling, currently available therapies, and ongoing obstacles in the field of colorectal cancer.
Insights
Molecular profiling improves metastatic colorectal cancer treatment by enabling targeted therapies. Further research is vital to overcome treatment resistance and enhance long-term survival for this deadly disease.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Metastatic colorectal cancer (mCRC) is a significant global health burden and a primary cause of cancer mortality.
- The treatment landscape for mCRC has evolved from traditional chemotherapy to incorporate targeted therapies and immunotherapies.
- Extensive research over the past two decades has focused on the molecular profiling of colorectal cancer.
Purpose of the Study:
- To provide a comprehensive review of molecular profiling in colorectal cancer.
- To evaluate current targeted therapies and immunotherapies for metastatic disease.
- To identify and discuss ongoing challenges and future directions in mCRC treatment.
Main Methods:
- Review of current literature on molecular profiling in colorectal cancer.
- Analysis of genetic pathways, including EGFR, VEGF, and HER2, and their role in targeted therapy development.
- Examination of National Comprehensive Cancer Network guidelines for colon and rectal cancer therapies.
Main Results:
- Molecular profiling enhances understanding of mCRC biology and facilitates personalized treatment strategies.
- Targeted therapies developed through pathway investigation (e.g., EGFR, VEGF, HER2, mismatch repair deficiency) are now standard in mCRC care.
- Despite advances, long-term survival for patients with metastatic colorectal cancer remains suboptimal.
Conclusions:
- Molecular profiling is crucial for tailoring treatments in metastatic colorectal cancer.
- Current targeted therapies have improved survival but have not fully addressed long-term outcomes.
- Further research into overcoming resistance mechanisms and developing novel targeted therapies is essential for improving patient survival.
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