| Autor: |
Centenera MM; Adelaide Medical School, University of Adelaide, North Terrace, Adelaide, SA 5000, Australia.; Freemasons Centre for Male Health and Wellbeing, University of Adelaide, North Terrace, Adelaide, SA 5000, Australia.; Precision Medicine Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia., Vincent AD; Adelaide Medical School, University of Adelaide, North Terrace, Adelaide, SA 5000, Australia.; Freemasons Centre for Male Health and Wellbeing, University of Adelaide, North Terrace, Adelaide, SA 5000, Australia., Moldovan M; Biometry Hub, Faculty of Science, University of Adelaide, Waite Campus, SA 5005, Australia., Lin HM; Garvan Institute for Medical Research, Darlinghurst, NSW 2010, Australia., Lynn DJ; Precision Medicine Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia.; Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA 5042, Australia., Horvath LG; Garvan Institute for Medical Research, Darlinghurst, NSW 2010, Australia.; Chris O'Brien Lifehouse, Camperdown, NSW 2050, Australia.; University of Sydney, Camperdown, NSW 2006, Australia., Butler LM; Adelaide Medical School, University of Adelaide, North Terrace, Adelaide, SA 5000, Australia.; Freemasons Centre for Male Health and Wellbeing, University of Adelaide, North Terrace, Adelaide, SA 5000, Australia.; Precision Medicine Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia. |
| Abstrakt: |
Prostate cancer is a complex and heterogeneous disease, but a small number of cell lines have dominated basic prostate cancer research, representing a major obstacle in the field of drug and biomarker discovery. A growing lack of confidence in cell lines has seen a shift toward more sophisticated pre-clinical cancer models that incorporate patient-derived tumors as xenografts or explants, to more accurately reflect clinical disease. Not only do these models retain critical features of the original tumor, and account for the molecular diversity and cellular heterogeneity of prostate cancer, but they provide a unique opportunity to conduct research in matched tumor samples. The challenge that accompanies these complex tissue models is increased complexity of analysis. With over 10 years of experience working with patient-derived explants (PDEs) of prostate cancer, this study provides guidance on the PDE method, its limitations, and considerations for addressing the heterogeneity of prostate cancer PDEs that are based on statistical modeling. Using inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) as an example of a drug that induces robust proliferative response, we demonstrate how multi-omics analysis in prostate cancer PDEs is both feasible and essential for identification of key biological pathways, with significant potential for novel drug target and biomarker discovery. |
