Development of in vitro and in vivo models of uveal melanoma

  • Research type

    Research Study

  • Full title

    Development of in vitro and in vivo models of uveal melanoma

  • IRAS ID

    203907

  • Contact name

    Sarah, E Coupland

  • Contact email

    s.e.coupland@liv.ac.uk

  • Sponsor organisation

    University of Liverpool

  • Clinicaltrials.gov Identifier

    CR1095, NWCR Grant

  • Duration of Study in the UK

    2 years, 3 months, 29 days

  • Research summary

    Uveal melanoma is a very rare type of adult eye cancer. In approximately 50% of individuals suffering from this cancer it will eventually spread to the liver, which is fatal.There are currently no effective treatments once the cancer has spread to the liver. To have a better understanding of and to be able to treat this, disease models are required that mimic the cancer. In this study we will use primary uveal melanoma cells isolated from patient tumour specimens to reflect the known molecular and clinical diversity. The aim will be to use these cells to develop in vitro and in vivo pre-clinical models, which reproduce aspects of the patient tumour and its microenvironment and that can be further used test new drugs and explore tumour biology.

    Lay Summary:
    This study examined the development of optimised conditions and protocols for cell dissemination from primary tumour tissue of patients diagnosed with uveal melanoma and propagation as 3D spheroids and 3D organoids embedded in a matrix. Organoid and 3D spheroid success rates varied depending on tumour condition such as the presence of necrotic tissue and the fibrotic nature of the tumour. Maintenance of organoids and continued growth was possible, in a small number of samples, however this diminished over the time grown in culture. 3D cultures were used at a single time point for drug assays. Organoid and 3D spheroid morphology matched that of the primary tumour, as did genetic copy number aberrations and genetic mutations. These results demonstrated the successful short term propagation of tumour cells in 3D that could be manipulated and assessed for their molecular and morphological characteristics as compared with the original patient tumour. Propagation to generate a 'living biobank' of tumour tissue for use in downstream assays was not achieved.

  • REC name

    London - Surrey Borders Research Ethics Committee

  • REC reference

    18/LO/1576

  • Date of REC Opinion

    11 Sep 2018

  • REC opinion

    Favourable Opinion