Culturing tumours in 3D assists cancer drug development

Porous polymer scaffolds fabricated to support the growth of biological tissue for implantation could accelerate the development of cancer therapeutics, researchers claim.

Researchers in the US have reported that 3D scaffolds used to culture Ewing’s sarcoma cells were effective at mimicking the environment in which such tumours develop.

‘The scaffolds better recapitulate the microenvironment in which tumours grow, as compared with two-dimensional plastic surfaces typically used in cancer research to test anti-cancer drugs,’ said Rice University bioengineer Antonios Mikos, who led the research team with Joseph Ludwig, an assistant professor and sarcoma medical oncologist at the University of Texas MD Anderson Cancer Center.

‘We’ve been working to investigate how we can leverage our expertise in engineering normal tissues to cancerous tissues, which can potentially serve as a better predictor of anti-cancer drug response than standard drug-testing platforms,’ Mikos said in a statement.

By growing cancer cells within a three-dimensional scaffold rather than on flat surfaces, the team of researchers found that the cells bore closer morphological and biochemical resemblance to tumours in the body.

Additionally, engineering tumours that mimic those in vivo offers opportunities to more accurately evaluate such strategies as chemotherapy or radiation therapies, he said.

The project provides a path forward to better evaluate promising biologically targeted therapies in the preclinical setting, Ludwig said.

Scaffolds fabricated in the Mikos’ lab are said to facilitate the development and growth of new tissue outside the body for subsequent implantation to replace defective tissues.

The team found 3D scaffolds to be a suitable environment for growing Ewing’s sarcoma, the second most-common paediatric bone malignancy. The tumour growth profile and protein expression characteristics were remarkably unlike those in 2D, Mikos said.

These differences led them to hypothesize that 2D cultures may mask the mechanisms by which tumours develop resistance to anti-cancer therapeutics, and may lead to erroneous scientific conclusions that complicate our understanding of cancer biology, they said.

The next challenge is to customise scaffolds to more accurately match the actual conditions in which these tumours are found.

‘Tumours in vivo exist within a complex microenvironment consisting of several other cell types and extracellular matrix components,’ Mikos said. ‘By taking the bottom-up approach and incorporating more components to this current model, we can add layers of complexities to make it increasingly reliable.

‘But we believe what we currently have is very promising,’ he said. ‘If we can build upon these results, we can potentially develop an excellent predictor of drug efficacy in patients.’

Their research, with input from Mount Sinai Medical Center in New York, appears online this week in the Proceedings of the National Academy of Sciences. The abstract can be found here.