دورية أكاديمية
Somatic Alterations Impact AR Transcriptional Activity and Efficacy of AR-Targeting Therapies in Prostate Cancer.
العنوان: | Somatic Alterations Impact AR Transcriptional Activity and Efficacy of AR-Targeting Therapies in Prostate Cancer. |
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المؤلفون: | Chauhan G; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, NB-40, 9500 Euclid Avenue, Cleveland, OH 44195, USA., Heemers HV; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, NB-40, 9500 Euclid Avenue, Cleveland, OH 44195, USA. |
المصدر: | Cancers [Cancers (Basel)] 2021 Aug 05; Vol. 13 (16). Date of Electronic Publication: 2021 Aug 05. |
نوع المنشور: | Journal Article; Review |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI |
مستخلص: | Inhibiting the activity of the ligand-activated transcription factor androgen receptor (AR) is the default first-line treatment for metastatic prostate cancer (CaP). Androgen deprivation therapy (ADT) induces remissions, however, their duration varies widely among patients. The reason for this heterogeneity is not known. A better understanding of its molecular basis may improve treatment plans and patient survival. AR's transcriptional activity is regulated in a context-dependent manner and relies on an interplay between its associated transcriptional regulators, DNA recognition motifs, and ligands. Alterations in one or more of these factors induce shifts in the AR cistrome and transcriptional output. Significant variability in AR activity is seen in both castration-sensitive (CS) and castration-resistant CaP (CRPC). Several AR transcriptional regulators undergo somatic alterations that impact their function in clinical CaPs. Some alterations occur in a significant fraction of cases, resulting in CaP subtypes, while others affect only a few percent of CaPs. Evidence is emerging that these alterations may impact the response to CaP treatments such as ADT, radiation therapy, and chemotherapy. Here, we review the contribution of recurring somatic alterations on AR cistrome and transcriptional output and the efficacy of CaP treatments and explore strategies to use these insights to improve treatment plans and outcomes for CaP patients. |
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معلومات مُعتمدة: | R01 CA166440 United States CA NCI NIH HHS; R01 CA248048 United States CA NCI NIH HHS; CA166440, CA248048 United States CA NCI NIH HHS; Falk Catalyst Award Medical Research Trust |
فهرسة مساهمة: | Keywords: biomarker; castration; castration-resistant; castration-sensitive; disease stratification; genomics; hormonal therapy; personalized medicine; somatic alterations |
تواريخ الأحداث: | Date Created: 20210827 Latest Revision: 20211109 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC8393938 |
DOI: | 10.3390/cancers13163947 |
PMID: | 34439101 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2072-6694 |
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DOI: | 10.3390/cancers13163947 |