Journal article

Patient-derived Models of Abiraterone- and Enzalutamide-resistant Prostate Cancer Reveal Sensitivity to Ribosome-directed Therapy

Mitchell G Lawrence, Daisuke Obinata, Shahneen Sandhu, Luke A Selth, Stephen Q Wong, Laura H Porter, Natalie Lister, David Pook, Carmel J Pezaro, David L Goode, Richard J Rebello, Ashlee K Clark, Melissa Papargiris, Jenna Van Gramberg, Adrienne R Hanson, Patricia Banks, Hong Wang, Birunthi Niranjan, Shivakumar Keerthikumar, Shelley Hedwards Show all



BACKGROUND: The intractability of castration-resistant prostate cancer (CRPC) is exacerbated by tumour heterogeneity, including diverse alterations to the androgen receptor (AR) axis and AR-independent phenotypes. The availability of additional models encompassing this heterogeneity would facilitate the identification of more effective therapies for CRPC. OBJECTIVE: To discover therapeutic strategies by exploiting patient-derived models that exemplify the heterogeneity of CRPC. DESIGN, SETTING, AND PARTICIPANTS: Four new patient-derived xenografts (PDXs) were established from independent metastases of two patients and characterised using integrative genomics. A panel of rationally selected d..

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Awarded by National Health and Medical Research Council of Australia

Awarded by Department of Health and Human Services acting through the Victorian Cancer Agency (CAPTIV Program)

Awarded by U.S. National Institutes of Health

Awarded by CASS Foundation

Awarded by MINIECO

Awarded by Cancer Australia


Funding Acknowledgements

This work was supported by funding from the National Health and Medical Research Council of Australia (fellowships to M.G.L. 1035721, G.P.R. 1102752, D.L.G. 1052904, and R.T. 1090204; project grant 1121057 to W.D.T., L.A.S., G.P.R., and R.T.; project grant 1138242 to G.P.R., W.D.T., L.F., S.S., A.A., L.A.S., and M.G.L.), Cancer Australia (project grant 1084546 to L.F., R.D.H., R.B.P, S.S., and G.P.R), the Department of Health and Human Services acting through the Victorian Cancer Agency (Early Career Seed grant to M.G.L. 13033, fellowships to L.F. MCRF16007, R.A.T. MCRF15023, CAPTIV Program), U.S. National Institutes of Health (R01CA174777 to S.M.D.), Prostate Cancer Foundation of Australia fellowship to S.S. (YIA2013), the Prostate Cancer Foundation (Young Investigator Awards to L.A.S., E.C., and R.Y.), Movember-Prostate Cancer Foundation (Challenge Award to S.M.D.), the CASS Foundation (Medical Science grant to M.L. 7139), MINIECO (Juan de la Cierva' fellowship to E.C. IJCI-2014-19129), the Peter MacCallum Cancer Foundation, the EJ Whitten Foundation, the Peter and Lyndy White Foundation, and TissuPath Pathology.