PracticeUpdate: Haematology & Oncology

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Identifying key molecular alterations in prostate cancer may help in diagnosis and prognosis M etabolic and proteomic alterations can be identified in biopsy specimens from patients with prostate cancer that enable

PracticeUpdate is guided by a world-renowned Editorial and Advisory Board that represents community practi- tioners and academic specialists with cross-disciplinary expertise. Editor-in-Chief Lee Schwartzberg MD FACP Associate Editors Isabel Cunningham MD Axel Grothey, MD Advisory Board Kimberly Blackwell MD, Roxana Dronca MD, Andre Goy MD, Annette Hasenburg Prof Dr med, David Henry MD, Eric Jonasch MD, Jeffrey Kirshner MD, FACP, Ruben Niesvizky MD, Howard Scher MD, Roger Stupp, MD Editorial Contributors Brandt Esplin MD PhD, EDITORIAL AUSTRALIA Managing Editor Anne Neilson anne.neilson@elsevier.com Editor Carolyn Ng carolyn.ng@elsevier.com Designer Jana Sokolovskaja j.sokolovskaja@elsevier.com Jeremy Jones MD, Jarushka Naidoo MD, Moshe Ornstein MD, Erin Schenk MD PhD PracticeUpdate.com is your online resource for in- depth insights and inside commentary that matter most to medical specialists. PracticeUpdate Haematology &Oncology brings you highlights of key local and international conferences, relevant and timely medical news, expert opinions and journal article reviews in a convenient print periodical. Content is guided by PracticeUpdate’s world-renowned editorial and advisory board members who represent community practitioners and academic specialists with cross-disciplinary expertise. The ideas and opinions expressed in this publication do not necessarily reflect those of the Publisher. Elsevier Australia will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein. Becauseofrapidadvances in themedicalsciences, in particular, independent verification of diagnoses and drug dosages should bemade. Please consult the full current Product Information before prescribing any medication mentioned in this publication. Although all advertising material is expected to conform to ethical (medical) standards, inclusion in this publication does not constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer. ISSN 2206-463X (Print) ISSN 2206-4648 (Online) ADVERTISING Fleur Gill fleur.gill@elsevier.com 02 9422 8572 Linnea Mitchell-Taverner l.mitchell@elsevier.com 02 9422 8587

the distinction between benign and malignant tissue, conclude results of a spectroscopy and microarray study. Margarita Fardilha, MD, of the University of Aveiro, Portugal, explained that prostate cancer remains a major health problem worldwide. Treat- ment is still a challenge for urologists, as well as the establishment of a clear prognosis. Prognosis is compromised by the lack of sensi- tivity and specificity of available markers. It is imperative to unravel prostate cancer biology to enable the identification of key molecular events and molecules that aid in diagnosis, prognosis, and the discovery of new therapeutic targets. Dr Fardilha and colleagues set out to identify metabolic and proteomic alterations that ena- ble the distinction between prostate benign and malignant tissue. Biopsies from prostate tumours and adjacent benign tissue from the central zone of the gland were obtained from eight patients. Prostate-specific antigen blood levels, prostate carcinoma stage (TNM), and Gleason score were determined in all patients. Each sample was divided and analysed using two approaches: infrared spectroscopy, anti- body microarray. These approaches allowed for analysis of the expression and phosphorylation state of 800 signalling proteins. The list of differentially expressed/regulated proteins between normal and tumour conditions was then subjected to an extensive bioinformatics analysis to inte- grate and complement all data with existing studies. Principal component analysis of spectroscopic signals derived from prostate cancer biopsies and adjacent benign tissues revealed different spectra for each condition. Dysregulations in lipid metabolism, lower amounts of polysaccharides and glycogen, as well as increased content of nucleic acids and protein phosphorylation were the most relevant alterations observed in prostate cancer tissues. Moreover, 40 proteins were identified as differ- entially expressed between the two conditions. Thirteen proteins revealed alterations in their phosphorylation levels. Identification of known prostate cancer-related

proteins reinforced the fidelity of the screen. Analysis of protein–protein interaction networks and ontologies showed disruption of cell signalling events during prostate carcinogenesis. Dr Fardilha concluded that metabolomics and proteomic approaches can provide vast informa- tion about carcinogenic processes. Integration of different “omic” approaches are increasingly important when moving to the era of person- alised medicine. This transition requires the understanding of disease as an entire, integrated pathophysiological process Dr Fardilha and coinvestigators showed that applying two distinct approaches to the same set of samples enables retrieval of a substantial amount of complementary information. Using these approaches not only increases the understanding of prostate carcinogenesis, but also allows for identification of key molecular alterations that may aid in accurate diagnosis/ prognosis and in the development of new, targeted therapies.

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