BIOTECHNOLOGY 51
D NEWIMENSION A
Biology is not fl at, so one expert in the sector is aiming to make 3D cell culture a commodity, explains Angel Garcia Martin
P
harma companies realise that most of the pre-clinical testing they
have been doing just isn’t good enough. As many as 9 in 10 drug candidates fail in clinical testing, and the majority of this attrition is due to toxicity and effi cacy issues. T is suggests that the translational tools currently used for predicting effi cacy and clinical response are not optimal. Pharma is reviving the ‘fail fast, fail cheap’ philosophy it used to try to improve pre- clinical and clinical testing outcomes in the setting of early- stage R&D and screening. Cells grown in the bottom of plastic plates as monolayer, 2D cell cultures have very diff erent expression patterns of genes, proteins and potential drug targets compared to what
those cells would be expressing in the body. In 2D culture, the cells are not exposed to the same mechanical infl uences, external signals or rates of diff usion, which can all aff ect gene expression. T ese factors can be simulated in 3D microtumours, such as switching from 2D to 3D cell models, and adopting more advanced testing methods earlier in the research workfl ow. Almost all the drug screening
eff orts carried out currently for discovering novel anti-cancer compounds rely on in vitro immortalised cancer cell line models grown in 2D, which have demonstrated a poor success in predicting clinical effi cacy, resulting in an alarming 95% failure after clinical testing, representing a waste of precious resources and time.
Over the past year-and-
a-half, we have seen a trend toward pharma wanting to model physiologically relevant tumour phenotypes to screen compounds. Biology is not fl at: cells, tissues, organs, even tumours, live in a 3D environment, thus it is desirable to test for novel compounds in systems that recreate the architecture and behaviour of cells in their natural 3D environment to understand how those compounds would behave in the natural setting. Pharma needs 3D tissue models that will better allow it to predict more accurately how a compound will function in humans. T e convenience,
availability and homogeneity of conventional continuous cell line models used for
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Models that better recapitulate the physiological features of human tumours are a step towards rational drug development
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