Clonal Evolution of MEK/MAPK Pathway Activating Mutations in a Metastatic Colorectal Cancer Case

Kaisa I Lehtomaki1,2, Laura I Lahtinen3, Nina Rintanen3

  • 1Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland kaisa.lehtomaki@tuni.fi.

Anticancer Research
|November 10, 2019
PubMed
Abstract

Insights

This study shows that liquid biopsy can track aggressive BRAF L597Q-mutated colorectal cancer (CRC) progression. Ex vivo drug screening identified MEK/MAPK targeted therapies as effective treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Investigating clonal heterogeneity in colorectal cancer (CRC).
  • Assessing liquid biopsy utility for monitoring disease progression.
  • Evaluating ex vivo drug screening in a BRAF L597Q-mutated CRC patient with metastatic disease during adjuvant therapy.

Observation:

  • Next-generation sequencing (NGS) and droplet digital PCR (ddPCR) analyzed tumor tissues and liquid biopsies.
  • Live cancer cells from metastases underwent ex vivo drug sensitivity assays.
  • MEK/MAPK pathway activation persisted, with distinct mutations in primary tumors versus metastases.

Findings:

  • Liquid biopsy-based BRAF L597Q ddPCR testing served as a sensitive biomarker for aggressive metastatic CRC.
  • Ex vivo drug sensitivity assays demonstrated that BRAF L597Q-mutated cells responded to MEK/MAPK targeted therapies.

Implications:

  • The rare BRAF L597Q mutation may indicate aggressive CRC behavior.
  • Liquid biopsy effectively captures clinically relevant tumor characteristics.
  • Ex vivo drug screening and liquid biopsy offer personalized treatment strategies for CRC.

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