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Updated: Jul 15, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Molecular response assessment using circulating tumor DNA (ctDNA) in advanced solid tumors
Jeffrey C Thompson1,2, Dylan G Scholes3,4, Erica L Carpenter5,3
1Division of Pulmonary, Allergy and Critical Care Medicine, Thoracic Oncology Group, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. jeffrey.thompson@pennmedicine.upenn.edu.
Abstract:
The therapeutic landscape for patients with advanced malignancies has changed dramatically over the last twenty years. The growing number of targeted therapies and immunotherapeutic options available have improved response rates and survival for a subset of patients, however determining which patients will experience clinical benefit from these therapies in order to avoid potential toxicities and reduce healthcare costs remains a clinical challenge. Cell-free circulating tumor DNA (ctDNA) is shed by tumor cells into systemic circulation and is already an integral part of routine clinical practice for the non-invasive tumor genotyping in advanced non-small cell lung cancer as well as other malignancies. The short half-life of ctDNA offers a unique opportunity to utilize early on-treatment changes in ctDNA for real-time assessment of therapeutic response and outcome, termed molecular response. Here, we provide a summary and review of the use of molecular response for the prediction of outcomes in patients with advanced cancer, including the current state of science, its application in clinic, and next steps for the development of this predictive tool.
Insights
Monitoring cell-free circulating tumor DNA (ctDNA) changes during treatment, known as molecular response, can predict patient outcomes in advanced cancers. This approach helps personalize therapy, reduce toxicity, and manage costs effectively.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cancer Therapeutics
Background:
- The treatment of advanced malignancies has evolved significantly with targeted therapies and immunotherapies, improving outcomes for some patients.
- Identifying patients likely to benefit from these treatments is crucial to minimize toxicity and healthcare expenses.
- Cell-free circulating tumor DNA (ctDNA) is a non-invasive biomarker used for tumor genotyping in various cancers.
Purpose of the Study:
- To review the predictive value of molecular response, defined by early on-treatment changes in ctDNA, for patient outcomes in advanced cancer.
- To summarize the current scientific understanding, clinical applications, and future directions for molecular response as a predictive tool.
Main Methods:
- Review of existing scientific literature on ctDNA and molecular response in advanced malignancies.
- Analysis of the application of ctDNA monitoring for real-time assessment of therapeutic response.
- Discussion of the potential of molecular response in predicting clinical benefit and patient outcomes.
Main Results:
- Early changes in ctDNA levels during treatment (molecular response) can serve as a sensitive indicator of therapeutic efficacy.
- ctDNA's short half-life allows for timely assessment of treatment response, unlike traditional methods.
- Molecular response has shown promise in predicting long-term outcomes for patients with advanced cancers.
Conclusions:
- Molecular response using ctDNA is a valuable tool for real-time prediction of treatment outcomes in advanced cancer.
- Further development and validation are needed to fully integrate molecular response into routine clinical practice for personalized cancer care.
- This approach holds potential for optimizing treatment strategies, reducing adverse effects, and improving patient survival.
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