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Androgen receptor gene and hormonal therapy failure of prostate cancer
P Koivisto1, M Kolmer, T Visakorpi
1Laboratory of Cancer Genetics, Tampere University Hospital and Institute of Medical Technology, University of Tampere, Finland.
Abstract:
Androgen receptor (AR) is a nuclear transcription factor that binds male sex steroids and mediates the biological effects of these hormones to the target cells, such as the epithelial cells of the prostate gland, by activating transcription of androgen-dependent genes. Withdrawal of androgens or the peripheral blockade of androgen action remain the critical therapeutic options for the treatment of advanced prostate cancer. However, after initial regression, many prostate cancers become hormone refractory and progress further with eventual fatal outcome. Understanding the mechanisms of tumor progression and endocrine therapy failure is an important goal. A large number of different molecular mechanisms may be responsible for development of hormone-refractory recurrent tumors. Many of these involve the AR gene and its complex downstream signaling pathways. The role of AR mutations and altered transactivational properties of the receptor have received the most attention as causative factors for progression. However, other mechanisms, such as AR gene amplification and overexpression or increased local bioconversion of androgens, may contribute to the development of progression by mechanisms that involve androgen-dependent cell growth. Here we review the role of the AR gene and its putative downstream effector pathways during human prostate cancer progression and endocrine therapy failure.
Insights
Androgen receptor (AR) signaling drives prostate cancer growth. Understanding AR gene alterations is key to overcoming hormone therapy resistance in advanced prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Androgen receptor (AR) is crucial for prostate cancer cell growth.
- Current treatments for advanced prostate cancer involve androgen withdrawal or blockade.
- Prostate tumors often develop resistance to endocrine therapy, leading to fatal progression.
Purpose of the Study:
- To review the molecular mechanisms underlying prostate cancer progression.
- To explore the role of the AR gene in endocrine therapy failure.
- To understand how AR signaling contributes to hormone-refractory tumors.
Main Methods:
- Literature review of studies on AR gene and prostate cancer progression.
- Analysis of molecular mechanisms driving endocrine therapy resistance.
- Examination of AR gene alterations and downstream signaling pathways.
Main Results:
- AR gene mutations and altered receptor activity are significant factors in progression.
- AR gene amplification and overexpression can also drive tumor growth.
- Increased local androgen production contributes to androgen-dependent growth in resistant tumors.
Conclusions:
- Multiple AR-related mechanisms contribute to prostate cancer progression and therapy failure.
- Targeting AR signaling pathways is critical for managing advanced prostate cancer.
- Further research into AR's role is essential for developing effective treatments.