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Understanding microRNA-Mediated Chemoresistance in Colorectal Cancer Treatment.

Guillermo Valenzuela1,2, Héctor R Contreras1,2, Katherine Marcelain1,2

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MicroRNAs (miRNAs) are crucial regulators impacting chemotherapy response in colorectal cancer (CRC). Understanding their role in chemoresistance offers new avenues for precision oncology and improved patient outcomes.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Colorectal cancer (CRC) is a leading cause of cancer death globally, with increasing incidence projected by 2040.
  • Current chemotherapy responses in CRC are highly variable, necessitating novel biomarkers for personalized treatment strategies.
  • MicroRNAs (miRNAs) are key post-transcriptional regulators influencing diverse cellular pathways relevant to cancer progression and drug response.

Purpose of the Study:

  • To review the role of microRNAs (miRNAs) in mediating chemoresistance in colorectal cancer (CRC).
  • To explore the potential of miRNAs as predictive biomarkers and therapeutic targets for overcoming treatment resistance in CRC.
  • To highlight challenges and future directions for the clinical translation of miRNA-based strategies in CRC oncology.

Main Methods:

  • Literature review focusing on the regulatory functions of miRNAs in CRC chemoresistance.
  • Analysis of miRNA involvement in drug transport (e.g., ABC transporters) and metabolic pathways (e.g., TYMS).
  • Examination of miRNA-mediated regulation of epithelial-mesenchymal transition (EMT) and its impact on chemosensitivity.

Main Results:

  • miRNAs critically modulate pathways associated with chemoresistance, including drug metabolism and transport.
  • Specific miRNAs (e.g., miR-200 family, miR-19a, miR-625-3p) demonstrate potential in reversing chemoresistance and predicting treatment outcomes.
  • miRNAs regulate EMT, a process linked to cancer stemness and therapeutic resistance in CRC.

Conclusions:

  • miRNAs play a significant role in the mechanisms of colorectal cancer chemoresistance.
  • miRNA-based biomarkers hold promise for guiding therapeutic decisions and improving patient stratification in CRC.
  • Further research addressing methodological challenges is needed to translate miRNA discoveries into clinical applications for precision oncology in CRC.