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Updated: Oct 13, 2025

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
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Plasma-Based Genotyping in Advanced Solid Tumors: A Comprehensive Review.

Maisam Makarem1, Miguel García-Pardo1, Natasha B Leighl1

  • 1Princess Margaret Cancer Center, Department of Medical Oncology, Toronto, ON M5G 2C1, Canada.

Cancers
|November 13, 2021
PubMed
Summary

Liquid biopsies using circulating tumor DNA (ctDNA) offer a powerful alternative for molecular genotyping in advanced cancers. This approach aids in selecting targeted therapies and managing treatment resistance when tissue biopsies are limited.

Keywords:
ctDNAguideline recommendationsplasma genotyping

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Area of Science:

  • Oncology
  • Molecular Diagnostics
  • Genomics

Background:

  • Molecular genotyping is crucial for targeted therapy selection in advanced solid malignancies.
  • Tumor tissue biopsies, the gold standard, are often limited or difficult to access.
  • This limitation necessitates alternative methods for genomic profiling.

Purpose of the Study:

  • To review the current and future applications of plasma ctDNA-based assays in advanced solid malignancies.
  • To highlight the role of ctDNA in guiding targeted therapy and diagnosing resistance.
  • To discuss the limitations of implementing plasma-based genomic testing in clinical practice.

Main Methods:

  • Review of recent advances in plasma-based circulating tumor DNA (ctDNA) detection.
  • Analysis of ctDNA assays for comprehensive genomic profiling in advanced cancers.
  • Examination of clinical guidelines recommending plasma-based testing.

Main Results:

  • Plasma-based ctDNA assays are increasingly integrated into clinical practice as an alternative or complementary tool.
  • These assays facilitate the identification of driver mutations for initial treatment selection.
  • ctDNA analysis aids in diagnosing treatment resistance in advanced cancer patients.

Conclusions:

  • Plasma ctDNA assays represent a significant advancement in molecular profiling for advanced solid tumors.
  • Guidelines now support plasma testing when tumor tissue is insufficient.
  • Further implementation of ctDNA-based assays in standard practice is anticipated, despite existing limitations.