On Wednesday 10th February, we attended the Laboratory Animal Sciences 2021 virtual event hosted by LabRoots, with this year’s theme being ‘From Theory to Practice, Tools & Considerations for Implementing the 3Rs’. The 3Rs initiative (Reduction, Refinement, Replacement) provides a framework for performing more humane animal research, and at Repositive, we are working towards facilitating this goal through the careful selection of CROs we choose to partner with. Below, we give you our key takeaways from the ‘Patient-Derived Organoids for Drug Development and Patient Stratification’ webinar given by Robert Vries, CEO of HUB Organoids, as part of the event.
For many years now, the cancer drug development paradigm has been suffering from problems with inefficiency and unpredictability, leading to very high levels of capital expenditure ($1.3 billion spent on average to bring a new drug to market) for results that 95% of the time lack translatability to human patients. By improving patient representation in preclinical modelling and culturing a closer relationship between the preclinical and clinical aspects of drug development, the system efficiency would increase significantly, leading to better results in the clinic and a reduction in associated costs.
HUB Organoids have put forward the concept of ‘a patient in the lab’, which proposes that in vitro cancer organoid models could be generated for any cancer patient, from almost any organ. This can be done by culturing patient stem cells from a tumour biopsy and using specific growth factors to stimulate their expansion, whilst ensuring maintenance of their genetic stability. This creates a culture system that is established to be a mimicry of the in-situ environment and therefore has functional resemblance to normal tissue, meaning cells can communicate with one another as if in normal epithelium. Co-culture systems can also be generated, for instance for investigating cancer immunotherapies, whereby the tumour microenvironment can be engineered to recreate key cellular components, such as immune cells, to observe the efficacy of immunotherapy tumour targeting in vitro.
Once an organoid model is established, the tissue can be characterised in terms of the following:
- Whole Genome DNA sequencing
- RNA sequencing
- Drug testing
- Personalised diagnostics
A direct correlation has been observed between patient drug responses in the clinic and the associated results seen in organoid models of their tumour, suggesting organoid technology is able to mimic the in-situ environment well and provide accurate data on how the patient is likely to respond to a treatment. As a result, organoid technology may be used to screen large cohorts of cancer patients for their response to a specific drug of interest, in order to identify individuals who will benefit most from the drug and those who should perhaps be considered for an alternative treatment regimen. Cancer is a time-sensitive disease and therefore, by enabling rapid patient stratification, organoid technology may be able to help match patients with drugs that are better suited to their specific tumour environment, and thus enable earlier treatment and better survival prospects.