Cell-Free RNA as a Novel Biomarker for Response to Therapy in Head & Neck Cancer
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 multipl...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.869108/full |
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| author | Anela Tosevska Anela Tosevska Marco Morselli Saroj K. Basak Luis Avila Parag Mehta Marilene B. Wang Marilene B. Wang Marilene B. Wang Eri S. Srivatsan Eri S. Srivatsan Eri S. Srivatsan Matteo Pellegrini Matteo Pellegrini Matteo Pellegrini |
| author_facet | Anela Tosevska Anela Tosevska Marco Morselli Saroj K. Basak Luis Avila Parag Mehta Marilene B. Wang Marilene B. Wang Marilene B. Wang Eri S. Srivatsan Eri S. Srivatsan Eri S. Srivatsan Matteo Pellegrini Matteo Pellegrini Matteo Pellegrini |
| author_sort | Anela Tosevska |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T01:27:14Z |
| format | Article |
| id | doaj.art-6e3890061d484d67b1592a3388577644 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-14T01:27:14Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-6e3890061d484d67b1592a33885776442022-12-22T02:20:22ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-05-011210.3389/fonc.2022.869108869108Cell-Free RNA as a Novel Biomarker for Response to Therapy in Head & Neck CancerAnela Tosevska0Anela Tosevska1Marco Morselli2Saroj K. Basak3Luis Avila4Parag Mehta5Marilene B. Wang6Marilene B. Wang7Marilene B. Wang8Eri S. Srivatsan9Eri S. Srivatsan10Eri S. Srivatsan11Matteo Pellegrini12Matteo Pellegrini13Matteo Pellegrini14Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA, United StatesDivision of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, AustriaDepartment of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA, United StatesDepartment of Surgery, Veterans Administration Greater Los Angeles Healthcare System, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, United StatesAveta Biomics Inc, Bedford, MA, United StatesAveta Biomics Inc, Bedford, MA, United StatesDepartment of Surgery, Veterans Administration Greater Los Angeles Healthcare System, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, United StatesDepartment of Head and Neck Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, United StatesJonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, United StatesDepartment of Surgery, Veterans Administration Greater Los Angeles Healthcare System, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, United StatesJonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, United StatesMolecular Biology Institute, University of California at Los Angeles, Los Angeles, CA, United StatesDepartment of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA, United StatesJonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, United StatesMolecular Biology Institute, University of California at Los Angeles, Los Angeles, CA, United StatesLiquid 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.869108/fullliquid biopsycfRNAhead & neckbiomarkerscurcumin |
| spellingShingle | Anela Tosevska Anela Tosevska Marco Morselli Saroj K. Basak Luis Avila Parag Mehta Marilene B. Wang Marilene B. Wang Marilene B. Wang Eri S. Srivatsan Eri S. Srivatsan Eri S. Srivatsan Matteo Pellegrini Matteo Pellegrini Matteo Pellegrini Cell-Free RNA as a Novel Biomarker for Response to Therapy in Head & Neck Cancer Frontiers in Oncology liquid biopsy cfRNA head & neck biomarkers curcumin |
| title | Cell-Free RNA as a Novel Biomarker for Response to Therapy in Head & Neck Cancer |
| title_full | Cell-Free RNA as a Novel Biomarker for Response to Therapy in Head & Neck Cancer |
| title_fullStr | Cell-Free RNA as a Novel Biomarker for Response to Therapy in Head & Neck Cancer |
| title_full_unstemmed | Cell-Free RNA as a Novel Biomarker for Response to Therapy in Head & Neck Cancer |
| title_short | Cell-Free RNA as a Novel Biomarker for Response to Therapy in Head & Neck Cancer |
| title_sort | cell free rna as a novel biomarker for response to therapy in head neck cancer |
| topic | liquid biopsy cfRNA head & neck biomarkers curcumin |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.869108/full |
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