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New strategies in prostate cancer: translating genomics into the clinic.

ABSTRACT: With the rapidly developing use of next-generation sequencing technologies, there has been a surge in our knowledge of the genomic landscape of prostate cancer and a movement toward developing a molecular subclassification system for the disease. With this new understanding comes great clinical potential, both for the development of biomarkers as well as new therapeutic targets. Herein, we highlight the potential clinical use of recent discoveries and how they fit into our current paradigm. We describe the challenges that lie ahead as we move from genomic sequencing toward routine clinical practice and adopt precision cancer care for patients with prostate cancer.

SUBMITTER: Beltran H

PROVIDER: S-EPMC4123124 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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New strategies in prostate cancer: translating genomics into the clinic.

Beltran Himisha H Rubin Mark A MA

Clinical cancer research : an official journal of the American Association for Cancer Research 20121217 3

With the rapidly developing use of next-generation sequencing technologies, there has been a surge in our knowledge of the genomic landscape of prostate cancer and a movement toward developing a molecular subclassification system for the disease. With this new understanding comes great clinical potential, both for the development of biomarkers as well as new therapeutic targets. Herein, we highlight the potential clinical use of recent discoveries and how they fit into our current paradigm. We d ...[more]

PMID: 23248095

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Project description:PurposeGleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management.Materials and methodsMembers of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes.ResultsThe Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes.ConclusionsThe definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

Project description:Simple Summary Breast cancer is the most common cancer affecting women, and the importance of NR function in breast cancer biology has been recognized since the turn of the 20th century. The nuclear receptor family of transcription factors is associated with cancer development and progression, informs diagnostic and prognostic outcomes, and is an established therapeutic target. Across all subtypes of breast cancer, crosstalk between NR pathways and other signalling pathways has also been demonstrated. Recent critical findings into modulating these NRs, particularly Type 1 NRs, have led to clinical trials and a greater understanding of their mechanism of action. Here, we reviewed the current preclinical insights into the role of Type 1 NRs in breast cancer that have served as a catalyst for clinical translation. Abstract The nuclear receptor (NR) family of transcription factors is intimately associated with the development, progression and treatment of breast cancer. They are used diagnostically and prognostically, and crosstalk between nuclear receptor pathways and growth factor signalling has been demonstrated in all major subtypes of breast cancer. The majority of breast cancers are driven by estrogen receptor α (ER), and anti-estrogenic therapies remain the backbone of treatment, leading to clinically impactful improvements in patient outcomes. This serves as a blueprint for the development of therapies targeting other nuclear receptors. More recently, pivotal findings into modulating the progesterone (PR) and androgen receptors (AR), with accompanying mechanistic insights into NR crosstalk and interactions with other proliferative pathways, have led to clinical trials in all of the major breast cancer subtypes. A growing body of evidence now supports targeting other Type 1 nuclear receptors such as the glucocorticoid receptor (GR), as well as Type 2 NRs such as the vitamin D receptor (VDR). Here, we reviewed the existing preclinical insights into nuclear receptor activity in breast cancer, with a focus on Type 1 NRs. We also discussed the potential to translate these findings into improving patient outcomes.

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New strategies in prostate cancer: translating genomics into the clinic.

Publications

New strategies in prostate cancer: translating genomics into the clinic.

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