SPHERMAR(TM): a 3D High Throughput Screening Platform for Anticancer Drug Discovery and Development
The SPHERMAR™ platform (Figure 1) has distinct advantages over other screening platforms since it creates high-throughput compatible 3D cultures that: are based on spontaneously-forming spheroids and thus do not require extraneous protocols to induce spheroidal morphology; retain the parent tumor phenotype and accurately mimic both in vivo metastasis (i.e. lymphovascular embolus) and the intratumoral biological complexities of the living tissue; are high yielding, simple (≤ 5 assay steps) and low cost; translate to a multiwall (>96) plate without the need for replacement or exchange of media or addition of molecular reagents to measure response; and produce reliable translational results in vivo
High throughput screening of drugs for relapsing and metastatic cancers.
By combining distinct features of the spheroidsMARY-X with a simple method for reading perturbation of the spheroid cohesiveness (i.e. dissolution index), the spheroid model has been transformed into a rapid, quantitative means to evaluate a drug’s dose-response curve. The screening ability of this platform, referred to as SPHERMARTM (see figure, below), is enabled by the observation that a drug’s induction of apoptosis correlates with the loss of well-circumscribed edges of the usually tight, compact spheroidsMARY-X where dissolution into a single cell population is consistent with cell death of the spheroid. Dissolution indices are determined through simple, brightfield image analysis of circularity (intact spheroid) vs. dissolution (single cell populations). The output of the SPHERMARTM platform is plotted as dose response curves which give reproducible and predictive IC50 values for anticancer drug screening and development.
State Of Development The SPHERMAR™ platform has been validated by in-house screening of two small-molecule libraries. Two promising anti-cancer compounds have been identified with IC50 values that correlate well to values derived from dual fluorescence assays. Intellectual Property Info Worldwide rights available; pending patents available under confidentiality. Issued US patent (6,998,513) is listed under “Patent Status”. Related Materials Theodoraki, M.A., et al. Spontaneously-forming spheroids as an in vitro cancer cell model for anticancer drug screening, 2015, Oncotarget, 2015 Jun 18. [Epub ahead of print]PMID:26101913 Tech ID/UC Case 25184/2015-153-0 Related Cases 2015-153-0, 1999-548-0
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