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Updated: Mar 29, 2026

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The Evolving Role for Repeat Molecular Testing in Metastatic Colorectal Cancer.

Nicholas D Kendsersky1, Mariah R Erlick1, Emerson Y Chen1

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Sequential biomarker testing in metastatic colorectal cancer (mCRC) aids in identifying resistance mechanisms and guiding subsequent treatments. Repeat testing post-progression is crucial for optimizing therapy and clinical trial selection.

Keywords:
ctDNAmetastatic colorectal cancernext-generation-sequencingprecision medicinesequential NGS

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Area of Science:

  • Oncology
  • Genomics
  • Translational Medicine

Background:

  • Next-generation sequencing (NGS) has transformed metastatic colorectal cancer (mCRC) treatment by enabling targeted and immune therapies.
  • Current guidelines (NCCN, ASCO) recommend initial biomarker testing (RAS, BRAF, HER2, MSI/MMR) for therapeutic eligibility.
  • Broader molecular profiling for tumor-agnostic therapies (TMB, NTRK, RET fusions) is encouraged in advanced solid tumors.

Purpose of the Study:

  • To review the advantages and disadvantages of sequential biomarker testing in mCRC patients during disease progression.
  • To highlight the role of repeat biomarker analysis in understanding adaptive resistance mechanisms.
  • To inform the development of unified guidelines for sequential testing in mCRC.

Main Methods:

  • Comprehensive literature review on sequential biomarker testing in mCRC.
  • Analysis of studies evaluating biomarker changes at disease progression.
  • Evaluation of current NCCN and ASCO recommendations.

Main Results:

  • NGS-driven therapies have improved outcomes in mCRC.
  • Repeat biomarker testing can reveal resistance mechanisms and guide subsequent treatment decisions.
  • Lack of unified guidelines for sequential biomarker testing presents a challenge.

Conclusions:

  • Sequential biomarker testing is essential for managing adaptive resistance in mCRC.
  • Repeat molecular profiling can optimize subsequent therapy selection and clinical trial enrollment.
  • Standardized guidelines are needed to facilitate consistent implementation of sequential biomarker testing.