4.6 Article

Ex Vivo Expanded Circulating Tumor Cells for Clinical Anti-Cancer Drug Prediction in Patients with Head and Neck Cancer

Journal

CANCERS
Volume 13, Issue 23, Pages -

Publisher

MDPI
DOI: 10.3390/cancers13236076

Keywords

circulating tumor cells; drug sensitivity; ex vivo expansion; head and neck cancer; response to therapy

Categories

Funding

  1. TMU Research Center of Cancer Translational Medicine from The Featured Areas Research Center Program within the Higher Education Sprout Project by theMinistry of Education (MOE) in Taiwan
  2. Ministry of Science and Technology [MOST 109-2635-B-038-001, MOST 109-2314-B-038122, MOST 109-2314-B-038-141, MOST 110-2320-B-038-056, MOST-110-2314-B-038-138]

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This study introduces a novel strategy to predict clinical drug responses in HNC patients by using eSelect, a lab-developed biomimetic cell culture system, allowing for ex vivo expansion and drug sensitivity profiling of circulating tumor cells (CTCs). Results show that the cisplatin sensitivity profiles of patient-derived CTCs expanded ex vivo correlate with a clinical response to cisplatin treatment, potentially providing predictive assays to guide HNC treatments.
Simple Summary The conventional methods that seek to predict clinical treatment response are based on the number of circulating tumor cells (CTCs) present in liquid biopsies or genetic profiling of extracted CTCs. This paper presents a novel process by which CTCs can be extracted from blood samples taken from head and neck cancer patients and then expanded ex vivo to form organoids that can be tested with a panel of anti-cancer treatments. The resulting drug sensitivity profiles derived from cisplatin treatment of organoids were subsequently found to correlate with clinical treatment response to cisplatin in patients. CTCs extracted from liquid biopsies for ex vivo expansion negates the need for complicated and potentially risky biopsies of tumor material, thereby supporting the application of this procedure for checkups and treatment monitoring. The advanced-stage head and neck cancer (HNC) patients respond poorly to platinum-based treatments. Thus, a reliable pretreatment method for evaluating platinum treatment response would improve therapeutic efficiency and outcomes. This study describes a novel strategy to predict clinical drug responses in HNC patients by using eSelect, a lab-developed biomimetic cell culture system, which enables us to perform ex vivo expansion and drug sensitivity profiling of circulating tumor cells (CTCs). Forty liquid biopsies were collected from HNC patients, and the CTCs were expanded ex vivo using the eSelect system within four weeks. Immunofluorescence staining confirmed that the CTC-derived organoids were positive for EpCAM and negative for CD45. Two illustrative cases present the potential of this strategy for evaluating treatment response. The statistical analysis confirmed that drug sensitivity in CTC-derived organoids was associated with a clinical response. The multivariant logistic regression model predicted that the treatment accuracy of chemotherapy responses achieved 93.75%, and the area under the curves (AUCs) of prediction models was 0.8841 in the whole dataset and 0.9167 in cisplatin specific dataset. In summary, cisplatin sensitivity profiles of patient-derived CTCs expanded ex vivo correlate with a clinical response to cisplatin treatment, and this can potentially underpin predictive assays to guide HNC treatments.

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