Researchers optimized spheroids from nine breast, ovarian and gastric cancer cell lines before comparing anticancer compounds. Some 3D models appeared more sensitive than their 2D counterparts, while others appeared less sensitive; exposure times also differed.
In ACS Omega, a BIOCAD-led team tested nine established cancer cell lines: the four breast-cancer lines BT-20, HCC70, MDA-MB-453 and T47D; the three ovarian-cancer lines TOV21G, A2780 and OVCAR-3; and the two gastric-cancer lines HGC-27 and SNU-1. Each line formed a separate spheroid monoculture. Most aggregated without an assembly aid, while TOV21G required agarose under the reported conditions.
Seeding, aggregate formation and assay timing were adapted to each cell line’s growth and medium quality. Treatment began after a reproducible single aggregate had formed, usually on day two or three. Spheroids received compounds for 14 or 21 days; the five lines also tested in 2D received 72 hours of treatment. Geometry and exposure duration therefore changed together, limiting attribution of an observed response difference to three-dimensional architecture alone.
The six reference agents were paclitaxel, cytarabine, 5-fluorouracil, oxaliplatin, etoposide and niraparib. Paclitaxel consistently inhibited viability across the spheroid panel below 100 nM and served as an assay performance control. AlamarBlue or PrestoBlue measurements were normalized to untreated wells under the corresponding model conditions.
The authors fitted concentration–response curves to estimate IC50 where the fit supported a reliable value. An integrated viability index summarized responses across the tested range, with a higher index indicating a stronger overall reduction in viability. It supplied a complementary measure when IC50 could not be reliably estimated; the two quantities were not interchangeable.
OVCAR-3, T47D and MDA-MB-453 showed greater apparent sensitivity to several agents in 3D than in 2D, whereas SNU-1 spheroids were generally less sensitive. A2780 changed direction according to the drug.
The researchers then tested in-house small molecules designed as CDK7 inhibitor candidates. Several reduced spheroid viability, and iCDK7_1 showed the most consistent activity across the tested models. The study measured antiproliferative responses; it did not establish CDK7 target engagement in every cell line or separate target effects from other causes of reduced metabolic viability.
Compound stability was not directly measured during the 14- or 21-day fixed-exposure assay. The study therefore supplies a practical example of cell-line-adapted comparative screening, with concentration and measurement method documented alongside the culture format.
A four-platform comparison combined lipid imaging, liver-function measurements, expression profiling and CYP assays. Lipid accumulation did not uniformly reduce drug metabolism, and differences depended on the model and donor.
A 512-compound screen in patient-derived motor neurons identified resveratrol tetramers with neuroprotective activity. Follow-up work covered 14 iPSC lines and linked protection to changes in neuronal excitability.
