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The Impact of Whole Genome Data on Therapeutic Decision-Making in Metastatic Prostate Cancer: A Retrospective Analysis.
Crumbaker, Megan; Chan, Eva K F; Gong, Tingting; Corcoran, Niall; Jaratlerdsiri, Weerachai; Lyons, Ruth J; Haynes, Anne-Maree; Kulidjian, Anna A; Kalsbeek, Anton M F; Petersen, Desiree C; Stricker, Phillip D; Jamieson, Christina A M; Croucher, Peter I; Hovens, Christopher M; Joshua, Anthony M; Hayes, Vanessa M.
Afiliación
  • Crumbaker M; Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
  • Chan EKF; St. Vincent's Clinical School, University of New South Wales, Sydney, Randwick NSW 2031, Australia.
  • Gong T; Kinghorn Cancer Centre, Department of Medical Oncology, St. Vincent's Hospital, Darlinghurst NSW 2010, Australia.
  • Corcoran N; Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
  • Jaratlerdsiri W; St. Vincent's Clinical School, University of New South Wales, Sydney, Randwick NSW 2031, Australia.
  • Lyons RJ; Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
  • Haynes AM; Central Clinical School, University of Sydney, Sydney, Camperdown NSW 2050, Australia.
  • Kulidjian AA; Australian Prostate Cancer Research Centre Epworth, Richmond VIC 3121, Australia.
  • Kalsbeek AMF; Department of Surgery, University of Melbourne, Melbourne VIC 3010, Australia.
  • Petersen DC; Division of Urology, Royal Melbourne Hospital, Melbourne VIC 3050, Australia.
  • Stricker PD; Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
  • Jamieson CAM; Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
  • Croucher PI; Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
  • Hovens CM; Department of Orthopedic Surgery, Scripps Clinic, La Jolla, CA 92037, USA..
  • Joshua AM; Orthopedic Oncology Program, Scripps MD Anderson Cancer Center, La Jolla CA 92037, USA.
  • Hayes VM; Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia.
Cancers (Basel) ; 12(5)2020 May 07.
Article en En | MEDLINE | ID: mdl-32392735
BACKGROUND: While critical insights have been gained from evaluating the genomic landscape of metastatic prostate cancer, utilizing this information to inform personalized treatment is in its infancy. We performed a retrospective pilot study to assess the current impact of precision medicine for locally advanced and metastatic prostate adenocarcinoma and evaluate how genomic data could be harnessed to individualize treatment. METHODS: Deep whole genome-sequencing was performed on 16 tumour-blood pairs from 13 prostate cancer patients; whole genome optical mapping was performed in a subset of 9 patients to further identify large structural variants. Tumour samples were derived from prostate, lymph nodes, bone and brain. RESULTS: Most samples had acquired genomic alterations in multiple therapeutically relevant pathways, including DNA damage response (11/13 cases), PI3K (7/13), MAPK (10/13) and Wnt (9/13). Five patients had somatic copy number losses in genes that may indicate sensitivity to immunotherapy (LRP1B, CDK12, MLH1) and one patient had germline and somatic BRCA2 alterations. CONCLUSIONS: Most cases, whether primary or metastatic, harboured therapeutically relevant alterations, including those associated with PARP inhibitor sensitivity, immunotherapy sensitivity and resistance to androgen pathway targeting agents. The observed intra-patient heterogeneity and presence of genomic alterations in multiple growth pathways in individual cases suggests that a precision medicine model in prostate cancer needs to simultaneously incorporate multiple pathway-targeting agents. Our whole genome approach allowed for structural variant assessment in addition to the ability to rapidly reassess an individual's molecular landscape as knowledge of relevant biomarkers evolve. This retrospective oncological assessment highlights the genomic complexity of prostate cancer and the potential impact of assessing genomic data for an individual at any stage of the disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Cancers (Basel) Año: 2020 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Cancers (Basel) Año: 2020 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Suiza