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Redefining Therapeutic Approaches in Colorectal Cancer: Targeting Molecular Pathways and Overcoming Resistance

Simona Gabriela Duta-Ion1, Ioana Ruxandra Juganaru1, Iulian Andrei Hotinceanu1

  • 1Department of Medical Genetics, "Carol Davila" University of Medicine and Pharmacy, 020021 Bucharest, Romania.

International Journal of Molecular Sciences
|December 17, 2024
PubMed

Insights

This review explores molecular pathways in colorectal cancer (CRC), focusing on genetic and epigenetic changes driving tumor growth. Understanding these mechanisms is key for personalized treatments and overcoming therapy resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Colorectal cancer (CRC) development is driven by complex genetic and epigenetic alterations.
  • Key molecular pathways critically influence tumor growth, progression, and treatment response.

Purpose of the Study:

  • To review major molecular pathways implicated in colorectal cancer (CRC).
  • To discuss the role of genetic mutations and epigenetic modifications in CRC tumorigenesis.
  • To explore targeted therapies and resistance mechanisms in CRC treatment.

Main Methods:

  • Literature review of major molecular pathways in CRC.
  • Analysis of key genetic mutations (APC, KRAS, NRAS, BRAF, TP53) and their associated signaling pathways (Wnt, EGFR, PI3K/AKT).
  • Examination of Chromosomal Instability (CIN), Microsatellite Instability (MSI), and CpG Island Methylator Phenotype (CIMP).

Main Results:

  • Genetic and epigenetic alterations activate critical signaling pathways driving CRC.
  • Mutations in key genes contribute to tumorigenesis and impact targeted therapy efficacy.
  • Mechanisms of therapeutic resistance, including bypass mutations, pose significant challenges.

Conclusions:

  • Molecular profiling is essential for guiding personalized targeted therapies in CRC.
  • Novel combination treatments offer strategies to enhance efficacy and overcome resistance.
  • A deep understanding of molecular mechanisms is crucial for improving CRC patient prognosis.
Keywords:
APC pathwayBRAF mutationsKRAS mutationsMSI/dMMRPI3K/AKT/mTOR pathwaycolon cancerimmunotherapytargeted therapy

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