Related Experiment Video

Updated: Feb 11, 2026

Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
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Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts

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Molecular Landscape of ERBB2/ERBB3 Mutated Colorectal Cancer

Jonathan M Loree1, Ann M Bailey2, Amber M Johnson2

  • 1Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Journal of the National Cancer Institute
|May 3, 2018
PubMed
Abstract

Insights

ERBB2 and ERBB3 mutations are found in colorectal cancer (CRC) and are associated with microsatellite instability and PIK3CA mutations. ERBB2 mutations correlate with worse overall survival in CRC patients.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Growing therapeutic relevance of ERBB2 amplifications in colorectal cancer (CRC).
  • Limited understanding of ERBB2/ERBB3 mutations in CRC.

Purpose of the Study:

  • To characterize ERBB2 and ERBB3 mutations in colorectal cancer.
  • To investigate associations between these mutations and clinicopathologic features, molecular subtypes, and survival outcomes.

Main Methods:

  • Retrospective analysis of three CRC cohorts (MD Anderson, NHS/HPFS, ctDNA).
  • Tissue sequencing, clinicopathologic, mutational, and consensus molecular subtype (CMS) profiling.
  • ctDNA assays for ERBB2 mutants.

Main Results:

  • ERBB2 mutations observed in 5.1%-5.8% and ERBB3 in 5.7% of CRC patients.
  • Microsatellite instability (MSI) and PIK3CA mutations significantly associated with ERBB2/ERBB3 mutations.
  • ERBB2 mutations linked to CMS1 subtype and worse overall survival.
  • ERBB3 mutations associated with CMS1 subtype but not survival.

Conclusions:

  • MSI and PIK3CA mutations are key correlates of ERBB2/ERBB3 mutations in CRC.
  • Co-occurring PIK3CA mutations may influence oncogenic signaling pathways targeted in ERBB2/ERBB3-mutant CRC.
  • These findings highlight potential therapeutic strategies for specific CRC subsets.

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