AI Article Synopsis
- Colorectal cancer (CRC) presents ongoing global health challenges, particularly in overcoming treatment resistance in cancer stem cells (CSCs) and the limitations of 5-fluorouracil (5-FU) therapy.
- Combination therapies and targeted treatments, such as FOLFOXIRI and various monoclonal antibodies, can boost the effectiveness of 5-FU, especially in specific tumor types, but come with considerable toxicity.
- Advances in personalized medicine, immunotherapy, and nanomedicine are vital for improving treatment outcomes by addressing the complexities of CRC and enhancing drug delivery while reducing resistance to conventional therapies.
Article Abstract
Colorectal cancer (CRC) remains a significant global health challenge, demanding continuous advancements in treatment strategies. This review explores the complexities of targeting colorectal cancer stem cells (CSCs) and the mechanisms contributing to resistance to 5-fluorouracil (5-FU). The efficacy of 5-FU is enhanced by combination therapies such as FOLFOXIRI and targeted treatments like bevacizumab, cetuximab, and panitumumab, particularly in KRAS wild-type tumors, despite associated toxicity. Biomarkers like thymidylate synthase (TYMS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) are crucial for predicting 5-FU efficacy and resistance. Targeting CRC-CSCs remains challenging due to their inherent resistance to conventional therapies, marker variability, and the protective influence of the tumor microenvironment which promotes stemness and survival. Personalized treatment strategies are increasingly essential to address CRC's genetic and phenotypic diversity. Advances in immunotherapy, including immune checkpoint inhibitors and cancer vaccines, along with nanomedicine-based therapies, offer promising targeted drug delivery systems that enhance specificity, reduce toxicity, and provide novel approaches for overcoming resistance mechanisms. Integrating these innovative strategies with traditional therapies may enhance the effectiveness of CRC therapy by addressing the underlying causes of 5-FU resistance in CSCs.
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| http://dx.doi.org/10.1016/j.ejphar.2025.177294 | DOI Listing |
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