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Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses
Published on: October 24, 2019
Revisiting nomenclature for the description of prostate cancer androgen-responsiveness
Hannelore V Heemers1, James L Mohler2
1Department of Urology, Roswell Park Cancer Institute Elm and Carlton Streets, Buffalo, NY 14263, USA ; Department of Cancer Genetics, Roswell Park Cancer Institute Elm and Carlton Streets, Buffalo, NY 14263, USA.
Abstract:
Ever since the Noble prize-winning findings of Huggins and Hodges, the androgen receptor (AR) has been the main target for treatment of advanced prostate cancer (CaP). Today, second- and even third-line androgen deprivation strategies, which have been designed rationally to interfere with the AR signaling that re-emerges under conditions of androgen deprivation and is at least in part responsible for disease recurrence, are effective in impeding progression of advanced CaP. The therapeutic success of these novel agents in CaP that has failed initial androgen deprivation therapy (ADT) and subsequent chemotherapy is prompting studies to explore their use earlier in the course of CaP progression. Repositioning of these drugs, along with alterations in the timing, sequencing and/or combination of traditional or novel ADTs, either alone or in combination with radiation or chemo- or immuno-therapies are expected to broaden significantly the scope of treatment options for CaP. Despite the rapidly changing and continuously innovating landscape of CaP therapies that target AR activity, the terminology that is used to describe CaP androgen status has not evolved. Currently available nomenclature falls short in capturing the sustained androgen-responsiveness of mostCaPs after ADT, does not distinguish readily between CaP's responsiveness to androgens and other steroid hormones, and does not specify the treatment condition(s) under which CaP recurs. A novel vocabulary is introduced to solve these limitations and to facilitate optimal communication among physicians, scientists and CaP patients.
Insights
Androgen receptor (AR) targeted therapies are advancing prostate cancer (CaP) treatment. A new vocabulary is proposed to better describe CaP androgen status and improve communication for advanced prostate cancer patients.
Area of Science:
- Oncology
- Urology
- Endocrinology
Background:
- The androgen receptor (AR) is a primary target for advanced prostate cancer (CaP) treatment.
- Current androgen deprivation strategies effectively manage AR signaling re-emergence and disease recurrence in advanced CaP.
- Novel AR-targeting agents show promise for earlier CaP treatment stages.
Purpose of the Study:
- To address limitations in current CaP terminology regarding androgen status.
- To introduce a novel vocabulary for improved communication among clinicians, researchers, and patients.
- To accurately capture CaP's sustained androgen-responsiveness and treatment context.
Main Methods:
- Review of existing CaP treatment strategies and terminology.
- Analysis of AR signaling pathways in advanced prostate cancer.
- Development and proposal of a new nomenclature for CaP androgen status.
Main Results:
- Existing terminology inadequately describes CaP's response to androgens and other hormones post-treatment.
- Current terms do not specify conditions under which CaP recurs.
- A novel vocabulary is presented to overcome these descriptive shortcomings.
Conclusions:
- A new vocabulary is essential for precise communication in advanced prostate cancer management.
- The proposed terminology will enhance understanding of CaP androgen status across different treatment scenarios.
- Improved communication facilitates better treatment decisions and patient care in advanced prostate cancer.
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