Blood, Toil, and Taxoteres: Biological Determinates of Treatment-Induce ctDNA Dynamics for Interpreting Tumor Response

Christopher T. Boniface, Paul T. Spellman

Research output: Contribution to journalReview articlepeer-review

Abstract

Collection and analysis of circulating tumor DNA (ctDNA) is one of the few methods of liquid biopsy that measures generalizable and tumor specific molecules, and is one of the most promising approaches in assessing the effectiveness of cancer care. Clinical assays that utilize ctDNA are commercially available for the identification of actionable mutations prior to treatment and to assess minimal residual disease after treatment. There is currently no clinical ctDNA assay specifically intended to monitor disease response during treatment, partially due to the complex challenge of understanding the biological sources of ctDNA and the underlying principles that govern its release. Although studies have shown pre- and post-treatment ctDNA levels can be prognostic, there is evidence that early, on-treatment changes in ctDNA levels are more accurate in predicting response. Yet, these results also vary widely among cohorts, cancer type, and treatment, likely due to the driving biology of tumor cell proliferation, cell death, and ctDNA clearance kinetics. To realize the full potential of ctDNA monitoring in cancer care, we may need to reorient our thinking toward the fundamental biological underpinnings of ctDNA release and dissemination from merely seeking convenient clinical correlates.

Original languageEnglish (US)
Article number1610103
JournalPathology and Oncology Research
Volume28
DOIs
StatePublished - May 19 2022

Keywords

  • biomarkers
  • circulating tumor DNA
  • ctDNA
  • liquid biopsy
  • treatment response
  • tumor growth

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oncology
  • Cancer Research

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