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Cell-free RNA as a Novel Biomarker for Response to Therapy in Head & Neck Cancer

ABSTRACT: Liquid biopsies are gaining more traction as non-invasive tools for the diagnosis and monitoring of cancer. A new class of cancer therapeutics, synergistic botanical drug combinations (APG-157) can target multiple pathways and provide a durable response and safety. Monitoring the efficacy of such drugs involves assessing multiple molecules and cellular events simultaneously. We report a methodology using plasma cell-free RNA (cfRNA) as an indicator of patient response during drug treatment. Plasma was collected from six patients with head and neck cancer (HNC) and four controls receiving 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. Analysis of the circulating transcriptome pointed to significant perturbations following APG-157 treatment. Transcripts associated with inflammatory response and leukocyte activation were upregulated upon treatment with APG-157 in cancer patients, but not in controls or placebo-treated patients. A platelet-related transcriptional signature could be detected in patients but not in controls, indicating a platelet-centric pathway in HNC. These results from a Phase 1 study are a proof of principle of the utility of cfRNAs as non-invasive biomarkers for monitoring the efficacy of APG-157 in HNC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196038 | GEO | 2022/04/05

REPOSITORIES: GEO

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