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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Recent developments in the treatment of metastatic colorectal cancer
Jonathan M Loree1, Scott Kopetz2
1Division of Gastrointestinal Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Abstract:
Over the past decade there have been significant advances in the molecular characterization of colorectal cancer (CRC) that are driving treatment decisions. Expanded RAS testing beyond KRAS exon 2 was established as crucial for identifying patients who will respond to anti-epidermal growth factor receptor (EGFR) therapies and low-frequency mutations in RAS/tumor heterogeneity are gaining recognition as potential mechanisms of resistance. Despite this progress, the fact that we do not understand why left-sided but not right-sided tumors have improved outcomes following anti-EGFR therapy highlights our superficial understanding of this disease. Even with few new targeted agents receiving approval in CRC, the incorporation of next-generation sequencing into clinical decision making represents an important step forward. Biomarkers such as BRAF mutations, microsatellite instability, and HER2 amplification represent promising molecular aberrations with therapies in various stages of development, and highlight the importance of companion diagnostics in supporting targeted agents. In this review, we will discuss the importance of incorporating biomarkers into clinical decision making and regimen selection in CRC. We will particularly focus on the recent evidence suggesting an important role for tumor location in selecting first-line therapy, the importance of recent advances in biomarker development and molecular subtyping, as well as recently approved agents (regorafenib and TAS-102) and promising targeted agents that have the potential to change the standard of care.
Insights
Molecular insights are transforming colorectal cancer (CRC) treatment. Biomarker testing, including RAS and BRAF mutations, guides targeted therapies, but tumor location
Area of Science:
- Oncology and Molecular Biology
- Translational Cancer Research
- Clinical Decision-Making in Oncology
Background:
- Significant advances in molecular characterization of colorectal cancer (CRC) are influencing treatment strategies.
- Expanded RAS testing beyond KRAS exon 2 is critical for anti-EGFR therapy response.
- Tumor heterogeneity and low-frequency mutations are recognized as resistance mechanisms, yet the impact of tumor location on anti-EGFR therapy outcomes remains unclear.
Purpose of the Study:
- To review the importance of incorporating biomarkers into clinical decision-making and regimen selection for CRC.
- To highlight recent advances in biomarker development, molecular subtyping, and their role in CRC treatment.
- To discuss the potential impact of tumor location and novel targeted agents on the standard of care for CRC.
Main Methods:
- Literature review focusing on molecular characterization of CRC.
- Analysis of recent evidence regarding biomarker utility in treatment selection.
- Discussion of approved and emerging targeted therapies and their associated diagnostics.
Main Results:
- Next-generation sequencing integration into clinical decision-making is a significant advancement.
- Biomarkers like BRAF mutations, microsatellite instability, and HER2 amplification are crucial for targeted therapy selection.
- Tumor location may play a significant role in determining first-line therapy efficacy.
Conclusions:
- Biomarker-driven therapy selection is essential for optimizing colorectal cancer treatment.
- Understanding molecular aberrations and tumor location is key to personalized CRC management.
- Novel targeted agents and companion diagnostics hold promise for improving CRC patient outcomes.
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