Recent Advances in Therapeutic Strategies to Improve Colorectal Cancer Treatment
1Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Abstract:
Colorectal cancer (CRC) is the second-leading cause of cancer-related mortality worldwide. CRC mortality results almost exclusively from metastatic disease (mCRC) for which systemic chemotherapy is often a preferred therapeutic option. Biomarker-based stratification of mCRC enables the use of precision therapy based on individual tumor mutational profiles. Activating mutations in the RAS/RAF/MAPK pathway downstream of EGFR signaling have, until recently, limited the use of EGFR-targeted therapies for mCRC; however, the development of anti-RAS and anti-RAF therapies together with improved strategies to limit compensatory signaling pathways is resulting in improved survival rates in several highly lethal mCRC sub-types (e.g., BRAF-mutant). The use of fluoropyrimidine (FP)-based chemotherapy regimens to treat mCRC continues to evolve contributing to improved long-term survival. Future advances in chemotherapy for mCRC will need to position development relative to the advances made in precision oncology.
Insights
Metastatic colorectal cancer (mCRC) treatment is advancing with precision therapies targeting tumor mutations and evolving chemotherapy regimens. These strategies are improving survival rates for patients with mCRC.
Area of Science:
- Oncology
- Genetics
Background:
- Colorectal cancer (CRC) is a leading cause of cancer mortality globally, primarily due to metastatic disease (mCRC).
- Systemic chemotherapy is a primary treatment for mCRC, with biomarker-based stratification enabling precision therapy.
- Activating mutations in the RAS/RAF/MAPK pathway historically limited EGFR-targeted therapies in mCRC.
Purpose of the Study:
- To review the evolving landscape of mCRC treatment.
- To highlight the impact of precision oncology and chemotherapy advancements on mCRC survival rates.
Main Methods:
- Review of current literature on mCRC treatment strategies.
- Analysis of biomarker-based stratification and targeted therapies.
- Evaluation of chemotherapy regimens and their integration with precision medicine.
Main Results:
- Development of anti-RAS and anti-RAF therapies, alongside strategies to manage compensatory signaling, has improved survival in specific mCRC subtypes (e.g., BRAF-mutant).
- Fluoropyrimidine (FP)-based chemotherapy regimens continue to evolve, contributing to enhanced long-term survival.
- Precision oncology approaches are increasingly important in managing mCRC.
Conclusions:
- Advances in targeted therapies and chemotherapy are significantly improving outcomes for mCRC patients.
- Future chemotherapy development for mCRC must align with progress in precision oncology.
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