Growing cancer cells in 3D -- not just 2D -- might improve preclinical drug development

One way to improve the success rate for new cancer drugs might be to test them in a three dimensional (3D) environment that mimics real life better than the two-dimensional (2D) set-up of a flat culture  dish, according to a new study that examined thousands of lung cancer proteins grown under both conditions.

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In the 3D culture, it is possible to simulate native cellular microenvironment, regular cell–cell interactions, cell–ECM interactions, and to test drugs with diffusion gradients. In the 2D culture cells can only form attachments to the substrate on their bottom side, have very few cell-cell interactions, no cell-ECM interactions and test drugs without diffusion gradients.

About 95 percent of experimental drugs for lung cancer fail in clinical trials, even after proving effective in preclinical laboratory tests. These preclinical tests typically occur in cells grown in a 2D model in a flat culture  dish. In patients, however, tumors grow in a 3D micro-environment that includes a blood supply and supporting structures (such as stroma). 

Scientists speculated that growing cancer cells in a 3D matrix might give a more accurate picture early on, before large investments of time and money in preclinical drug development. Supporting this idea is new research led by Josip Blonder, M.D., emeritus scientist at Frederick National Laboratory and published recently in Oncotarget.

Blonder and his colleagues grew lung cancer cells from a standard cancer cell line (NCI-H23) in 2D conventional culture  dishes and a 3D scaffold.

From these colonies, the scientists identified 4,180 protein groups in the 2D colony and 4,444 in the 3D population. A total of 1,166 protein groups were active in a way that depended on which type of culture they were grown in.  Of these, 334 were identified exclusively in cells grown in 3D culture and 598 identified solely in 2D cultured cells.

“It’s very important to have the information about the phenotypical differences induced solely by a given cell culture, so you can find out what’s going on prior to a given drug testing,” Blonder said. “The current data provide a proof-of-principle for the value of bridging the gap between conventional 2D in vitro cultures and in vivo animal testing models."

In fact, Blonder suggested that 3D-cultured cells may ultimately provide an alternative to using animal models in preclinical drug development.