Cell-Free RNA as a Novel Biomarker for Response to Therapy in Head & Neck Cancer
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Updated: Sep 22, 2025
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Anela Tosevska1,2, Marco Morselli1, Saroj K Basak3
1Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA, United States.
Abstract:
Liquid biopsies are gaining more traction as non-invasive tools for the diagnosis and monitoring of cancer. In a new paradigm of cancer treatment, a synergistic botanical drug combination (APG-157) consisting of multiple molecules, is emerging as a new class of cancer therapeutics, targeting multiple pathways and providing a durable clinical response, wide therapeutic window and high level of safety. Monitoring the efficacy of such drugs involves assessing multiple molecules and cellular events simultaneously. We report, for the first time, a methodology that uses circulating plasma cell-free RNA (cfRNA) as a sensitive indicator of patient response upon drug treatment. Plasma was collected from six patients with head and neck cancer (HNC) and four healthy controls receiving three doses of 100 or 200 mg APG-157 or placebo through an oral mucosal route, before treatment and on multiple points post-dosing. Circulating cfRNA was extracted from plasma at 0-, 3- and 24-hours post-treatment, followed by RNA sequencing. We performed comparative analyses of the circulating transcriptome and were able to detect significant perturbation following APG-157 treatment. Transcripts associated with inflammatory response, leukocyte activation and cytokine were upregulated upon treatment with APG-157 in cancer patients, but not in healthy or placebo-treated patients. A platelet-related transcriptional signature could be detected in cancer patients but not in healthy individuals, indicating a platelet-centric pathway involved in the development of HNC. These results from a Phase 1 study are a proof of principle of the utility of cfRNAs as non-invasive circulating biomarkers for monitoring the efficacy of APG-157 in HNC.
Insights
This study introduces circulating cell-free RNA (cfRNA) as a novel biomarker to monitor the effectiveness of APG-157, a new botanical cancer drug. This non-invasive method shows promise for tracking treatment response in head and neck cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Liquid biopsies are increasingly used for non-invasive cancer diagnosis and monitoring.
- Synergistic botanical drug combinations like APG-157 offer a new therapeutic approach targeting multiple cancer pathways.
- Monitoring the efficacy of multi-target drugs requires simultaneous assessment of molecular and cellular events.
Purpose of the Study:
- To establish a methodology using circulating cell-free RNA (cfRNA) as a sensitive indicator of patient response to APG-157 treatment.
- To investigate the utility of cfRNAs as non-invasive circulating biomarkers for monitoring APG-157 efficacy in head and neck cancer (HNC).
Main Methods:
- Plasma samples were collected from HNC patients and healthy controls before and after APG-157 or placebo administration.
- Circulating cfRNA was extracted at multiple time points post-treatment and analyzed using RNA sequencing.
- Comparative analyses of the circulating transcriptome were performed to identify treatment-induced changes.
Main Results:
- Significant perturbations in the circulating transcriptome were detected following APG-157 treatment in cancer patients.
- Transcripts related to inflammatory response, leukocyte activation, and cytokines were upregulated post-treatment.
- A distinct platelet-related transcriptional signature was identified in HNC patients, suggesting a role in disease development.
Conclusions:
- Circulating cfRNA serves as a sensitive, non-invasive biomarker for monitoring APG-157 efficacy in HNC patients.
- The study demonstrates the potential of cfRNA to track drug response and provides insights into HNC-associated pathways.
- This proof-of-principle study validates cfRNAs as valuable tools in cancer therapeutic monitoring.
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