Drug Discovery


The growth of organoids


in cancer drug discovery Will the automated expansion of organoids help improve the productivity of cancer drug discovery?


Increasingly, complex cell-based assays and tissues are routinely used as part of cancer drug discovery. However, conventional monolayer or suspension cultures can be poorly predictive of the relevant therapeutic effects on a patient’s tumour. As a result, many apparently attractive new drug candidates subsequently fail to meet their primary endpoints in clinical trials. Tumour- derived organoids have the potential to be more predictive earlier in discovery and thus reduce the high rate of compound attrition in downstream development. Tumour-derived organoids have typically been produced in small volumes in specialist research laboratories, using labour-intensive manual processes. Production capacity is constrained and there can be significant batch-to-batch variation. Scalable bioprocessing technologies for the expansion of organoids are now emerging to overcome the bottlenecks of these conventional manual processes. This article will review the challenges and solutions required to expand human cancer organoids to meet the growing demand for the large-scale production of organoids in drug discovery.


By Dr J. Mark Treherne,


Dr Marianne Ellis, Professor Trevor Dale, Dr Luned Badder and


Dr Andrew Hollins A 8


ccording to the World Health Organisation, cancer was the second leading cause of death, accounting for 8.8 million deaths


worldwide in 2015, with the number of new cancer cases expected to rise by 70% over the next two decades. Although historic investment in research has resulted in improved cancer survival rates over- all, not all forms of the disease have seen such progress and, for some cancers, long-term survival rates have not changed for decades. Consequently, there is an urgent and unmet need for the discovery of novel improved treatments. More than most other industries, the pharma- ceutical sector is highly dependent on the produc-


tivity of its research and development (R&D) expenditure to source innovative solutions for their needs, often investing 20% of their revenues back into research each year. Despite these unprecedent- ed levels of investment, current drug pipelines do not always meet the growth expectations of their shareholders for discovering cost-effective new therapies. This increasing pressure on the need to improve industrial productivity is largely due to high levels of pipeline attrition, which is an issue for anticancer drug development with approxi- mately 90% of drugs tested in clinical trials not meeting their primary endpoints. Therefore, the successful products that make it on to the market


Drug Discovery World Winter 2018/19


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