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  3. Identification of potential therapeutic targets in prostate cancer through a cross-species approach

Identification of potential therapeutic targets in prostate cancer through a cross-species approach

  • EMBO Mol Med. 2018 Mar;10(3):e8274. doi: 10.15252/emmm.201708274.
Sarah Jurmeister 1,  Antonio Ramos-Montoya 2,  Chiranjeevi Sandi 2,  Nelma Pértega-Gomes 3,  Karan Wadhwa 2,  Alastair D Lamb 2 4 5,  Mark J Dunning 6,  Jan Attig 7 8,  Jason S Carroll 9,  Lee Gd Fryer 2,  Sérgio L Felisbino 10,  David E Neal 2 4 5
Affiliations

Affiliations

  • 1 Uro-oncology Research Group, CRUK Cambridge Institute, Cambridge, UK [email protected].
  • 2 Uro-oncology Research Group, CRUK Cambridge Institute, Cambridge, UK.
  • 3 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • 4 Department of Urology, University of Cambridge, Cambridge, UK.
  • 5 Department of Oncology, Addenbrooke's Hospital, Cambridge, UK.
  • 6 Bioinformatics Core Facility, CRUK Cambridge Institute, Cambridge, UK.
  • 7 Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
  • 8 MRC-Laboratory of Molecular Biology, Cambridge, UK.
  • 9 Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • 10 Department of Morphology, Institute of Biosciences of Botucatu, Sao Paulo State University (UNESP), Sao Paulo, Brazil.
PMID: 29437778 DOI: 10.15252/emmm.201708274
Abstract

Genetically engineered mouse models of Cancer can be used to filter genome-wide expression datasets generated from human tumours and to identify gene expression alterations that are functionally important to Cancer development and progression. In this study, we have generated RNAseq data from tumours arising in two established mouse models of prostate Cancer, PB-Cre/PTENloxP/loxP and p53loxP/loxPRbloxP/loxP, and integrated this with published human prostate Cancer expression data to pinpoint cancer-associated gene expression changes that are conserved between the two species. To identify potential therapeutic targets, we then filtered this information for genes that are either known or predicted to be druggable. Using this approach, we revealed a functional role for the kinase MELK as a driver and potential therapeutic target in prostate Cancer. We found that MELK expression was required for cell survival, affected the expression of genes associated with prostate Cancer progression and was associated with biochemical recurrence.

Keywords

MELK; cross‐species analysis; mouse models; new cancer targets; prostate cancer.

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