Prostate cancer: Molecular aspects, consequences, and opportunities of the multifocal nature.

Autor: Skotheim RI; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Department of Informatics, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway. Electronic address: rolfis@uio.no., Bogaard M; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Department of Pathology, Oslo University Hospital, Oslo, Norway., Carm KT; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Axcrona U; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Department of Pathology, Oslo University Hospital, Oslo, Norway., Axcrona K; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Department of Urology, Akershus University Hospital, Lørenskog, Norway.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Reviews on cancer [Biochim Biophys Acta Rev Cancer] 2024 Mar; Vol. 1879 (2), pp. 189080. Date of Electronic Publication: 2024 Jan 24.
DOI: 10.1016/j.bbcan.2024.189080
Abstrakt: Prostate cancer is unique compared to other major cancers due to the presence of multiple primary malignant foci in the majority of patients at the time of diagnosis. Each malignant focus has distinct somatic mutations and gene expression patterns, which represents a challenge for the development of prognostic tests for localized prostate cancer. Additionally, the molecular heterogeneity of advanced prostate cancer has important implications for management, particularly for patients with metastatic and locally recurrent cancer. Studies have shown that prostate cancers with mutations in DNA damage response genes are more sensitive to drugs inhibiting the poly ADP-ribose polymerase (PARP) enzyme. However, testing for such mutations should consider both spatial and temporal heterogeneity. Here, we summarize studies where multiregional genomics and transcriptomics analyses have been performed for primary prostate cancer. We further discuss the vast interfocal heterogeneity and how prognostic biomarkers and a molecular definition of the index tumor should be developed. The concept of focal treatments in prostate cancer has been evolving as a demand from patients and clinicians and is one example where there is a need for defining an index tumor. Here, biomarkers must have proven value for individual malignant foci. The potential discovery and implementation of biomarkers that are agnostic to heterogeneity are also explored as an alternative to multisample testing. Thus, deciding upon whole-organ treatment, such as radical prostatectomy, should depend on information from biomarkers which are informative for the whole organ.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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