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Osteosarcoma in Children: Not Only Chemotherapy
Article

Assessing a Novel 3D Assay System for Drug Screening against OS Metastasis

1
Surgery Department, Massachusetts Veterinary Referral Hospital, Woburn, MA 01801, USA
2
Vuja De Sciences, Inc., Natick, MA 01760, USA
3
Department of Human Biology and Medical Sciences, University of Haifa, Haifa 3498838, Israel
4
Ethos Discovery, Woburn, MA 01801, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: See-Hyoung Park
Pharmaceuticals 2021, 14(10), 971; https://doi.org/10.3390/ph14100971
Received: 1 September 2021 / Revised: 21 September 2021 / Accepted: 23 September 2021 / Published: 25 September 2021
(This article belongs to the Special Issue Osteosarcomas: Treatment Strategies)
Osteosarcoma (OS) is an aggressive mesenchymal cell tumor that carries a poor long-term prognosis. Despite definitive surgery for the primary tumor and adjuvant chemotherapy, pulmonary metastasis is common and is the primary cause of morbidity. To improve outcomes for patients, we have developed and optimized a phenotypic screen for drugs that may target OS disseminated tumor cells (DTCs) and inhibit their metastatic outbreak rather than merely screening for cytotoxic activity against proliferating cells, as is commonly conducted in conventional drug discovery approaches. We report on the validation of a previously described 3D reconstituted basement membrane extract (3D BME) model system for tumor dormancy and metastatic outgrowth adapted to clonal pairs of high and low metastatic OS cells. A post-hoc validation of the assay was possible by comparing the activity of a drug in our assay with early evidence of activity in human OS clinical trials (regorafenib and saracatinib). In this validation, we found concordance between our assay and human clinical trial experience We then explored an approved veterinary small molecule inhibitor of Janus kinase-1 (oclacitinib) as a potential drug candidate to take advantage of the high prevalence of OS in pet dogs and its translational value to humans. Despite the biological rationale, we found no evidence to support the use of oclacitinib as an antimetastatic agent in OS. The findings support our 3D BME assay as a highly efficient method to examine drugs for activity in targeting OS DTCs. View Full-Text
Keywords: osteosarcoma; metastatic endurance; small molecule inhibitors; oclacitinib; regorafenib; saracatinib; basement membrane extract assay osteosarcoma; metastatic endurance; small molecule inhibitors; oclacitinib; regorafenib; saracatinib; basement membrane extract assay
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MDPI and ACS Style

Koons, N.; Amato, N.; Sauer, S.; Warshawsky, D.; Barkan, D.; Khanna, C. Assessing a Novel 3D Assay System for Drug Screening against OS Metastasis. Pharmaceuticals 2021, 14, 971. https://doi.org/10.3390/ph14100971

AMA Style

Koons N, Amato N, Sauer S, Warshawsky D, Barkan D, Khanna C. Assessing a Novel 3D Assay System for Drug Screening against OS Metastasis. Pharmaceuticals. 2021; 14(10):971. https://doi.org/10.3390/ph14100971

Chicago/Turabian Style

Koons, Natalie, Nicole Amato, Scott Sauer, David Warshawsky, Dalit Barkan, and Chand Khanna. 2021. "Assessing a Novel 3D Assay System for Drug Screening against OS Metastasis" Pharmaceuticals 14, no. 10: 971. https://doi.org/10.3390/ph14100971

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