Related Experiment Video
Updated: Nov 17, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
A standing platform for cancer drug development using ctDNA-based evidence of recurrence
Arielle J Medford1,2, Ariel B Carmeli3, Alexandra Ritchie3
1Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA.
Abstract:
The time required to conduct clinical trials limits the rate at which we can evaluate and deliver new treatment options to patients with cancer. New approaches to increase trial efficiency while maintaining rigor would benefit patients, especially in oncology, in which adjuvant trials hold promise for intercepting metastatic disease, but typically require large numbers of patients and many years to complete. We envision a standing platform - an infrastructure to support ongoing identification and trial enrolment of patients with cancer with early molecular evidence of disease (MED) after curative-intent therapy for early-stage cancer, based on the presence of circulating tumour DNA. MED strongly predicts subsequent recurrence, with the vast majority of patients showing radiographic evidence of disease within 18 months. Such a platform would allow efficient testing of many treatments, from small exploratory studies to larger pivotal trials. Trials enrolling patients with MED but without radiographic evidence of disease have the potential to advance drug evaluation because they can be smaller (given high probability of recurrence) and faster (given short time to recurrence) than conventional adjuvant trials. Circulating tumour DNA may also provide a valuable early biomarker of treatment effect, which would allow small signal-finding trials. In this Perspective, we discuss how such a platform could be established.
Insights
Accelerating cancer treatment evaluation requires innovative clinical trial designs. A new platform using circulating tumor DNA to identify patients with molecular evidence of disease (MED) could enable faster, smaller trials for new cancer therapies.
Area of Science:
- Oncology
- Clinical Trial Design
- Biomarkers
Background:
- Clinical trials are lengthy, delaying new cancer treatments.
- Adjuvant trials for early-stage cancer are crucial but often require large patient numbers and long durations.
- Molecular evidence of disease (MED) predicts recurrence, offering a potential window for intervention.
Purpose of the Study:
- To propose a standing platform infrastructure for identifying and enrolling patients with early molecular evidence of disease (MED) after curative-intent therapy.
- To enable efficient testing of multiple cancer treatments, from exploratory to pivotal trials.
- To leverage circulating tumor DNA (ctDNA) as a biomarker for patient selection and treatment response.
Main Methods:
- Envisioning a platform for ongoing identification and enrollment of cancer patients with MED based on ctDNA presence.
- Utilizing ctDNA to detect minimal residual disease after initial treatment.
- Designing trials for patients with MED but no radiographic evidence of disease.
Main Results:
- MED, detected via ctDNA, strongly predicts cancer recurrence within 18 months.
- Trials enrolling patients with MED could be smaller and faster than conventional adjuvant trials.
- ctDNA may serve as an early biomarker for treatment efficacy, facilitating signal-finding studies.
Conclusions:
- A standing platform utilizing ctDNA for MED detection can significantly enhance clinical trial efficiency in oncology.
- This approach allows for rapid evaluation of novel therapies in early-stage cancer patients at high risk of recurrence.
- Implementing such a platform could accelerate the delivery of effective cancer treatments to patients.
