Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer.
Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer.
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DOI：
10.3389/fendo.2022.1006101
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发表时间：
2022
影响因子：
5.2
通讯作者：
Jeyapalan, Jennie N.
中科院分区：
文献类型：
--
作者：
Harris, Anna E.;Metzler, Veronika M.;Lothion-Roy, Jennifer;Varun, Dhruvika;Woodcock, Corinne L.;Haigh, Daisy B.;Endeley, Chantelle;Haque, Maria;Toss, Michael S.;Alsaleem, Mansour;Persson, Jenny L.;Gudas, Lorraine J.;Rakha, Emad;Robinson, Brian D.;Khani, Francesca;Martin, Laura M.;Moyer, Jenna E.;Brownlie, Juliette;Madhusudan, Srinivasan;Allegrucci, Cinzia;James, Victoria H.;Rutland, Catrin S.;Fray, Rupert G.;Ntekim, Atara;de Brot, Simone;Mongan, Nigel P.;Jeyapalan, Jennie N.
关键词：
雄激素剥夺治疗（ADT）是通过阻止雄激素生物合成（例如阿比特龙）或拮抗雄激素受体（AR）功能（例如比卡鲁胺、恩杂鲁胺、达罗鲁米特）抑制雄激素诱导的前列腺癌（PCa）进展的重要治疗。目前ADT的一个主要限制是它们通常在有限的时间内保持有效，之后患者通常进展为致命且不可治愈的PCa形式，称为去势抵抗性前列腺癌（CRPC），其中AR继续协调促癌信号传导。事实上，ADT相关的治疗后出现的神经内分泌样前列腺癌（NePC）数量不断增加，缺乏AR，因此对ADT不敏感，这是一个主要的治疗挑战。因此，迫切需要更好地了解AR在激素依赖性疾病中的作用机制以及CRPC的进展，以开发预防、逆转或延迟ADT耐药性的新方法。有趣的是，AR调节激素依赖性和CRPC中不同的转录网络，这似乎与关键AR表观遗传辅调节酶（包括赖氨酸脱甲基酶1（LSD 1/KDM 1A））的异常功能有关。在这篇综述中，我们总结了目前抗雄激素临床试验的最佳状态，新的联合治疗的潜力，我们探讨了新的表观遗传靶向治疗的发展，可能与预防或逆转晚期CRPC患者的疾病进展。
Androgen deprivation therapies (ADTs) are important treatments which inhibit androgen-induced prostate cancer (PCa) progression by either preventing androgen biosynthesis (e.g. abiraterone) or by antagonizing androgen receptor (AR) function (e.g. bicalutamide, enzalutamide, darolutamide). A major limitation of current ADTs is they often remain effective for limited durations after which patients commonly progress to a lethal and incurable form of PCa, called castration-resistant prostate cancer (CRPC) where the AR continues to orchestrate pro-oncogenic signalling. Indeed, the increasing numbers of ADT-related treatment-emergent neuroendocrine-like prostate cancers (NePC), which lack AR and are thus insensitive to ADT, represents a major therapeutic challenge. There is therefore an urgent need to better understand the mechanisms of AR action in hormone dependent disease and the progression to CRPC, to enable the development of new approaches to prevent, reverse or delay ADT-resistance. Interestingly the AR regulates distinct transcriptional networks in hormone dependent and CRPC, and this appears to be related to the aberrant function of key AR-epigenetic coregulator enzymes including the lysine demethylase 1 (LSD1/KDM1A). In this review we summarize the current best status of anti-androgen clinical trials, the potential for novel combination therapies and we explore recent advances in the development of novel epigenetic targeted therapies that may be relevant to prevent or reverse disease progression in patients with advanced CRPC.
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影响因子：
82.9
作者：
Beltran H;Prandi D;Mosquera JM;Benelli M;Puca L;Cyrta J;Marotz C;Giannopoulou E;Chakravarthi BV;Varambally S;Tomlins SA;Nanus DM;Tagawa ST;Van Allen EM;Elemento O;Sboner A;Garraway LA;Rubin MA;Demichelis F
通讯作者：
Demichelis F
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
82.9
作者：
Dai X;Gan W;Li X;Wang S;Zhang W;Huang L;Liu S;Zhong Q;Guo J;Zhang J;Chen T;Shimizu K;Beca F;Blattner M;Vasudevan D;Buckley DL;Qi J;Buser L;Liu P;Inuzuka H;Beck AH;Wang L;Wild PJ;Garraway LA;Rubin MA;Barbieri CE;Wong KK;Muthuswamy SK;Huang J;Chen Y;Bradner JE;Wei W
通讯作者：
Wei W
DOI：
10.1158/1078-0432.ccr-13-3309
发表时间：
2014-06-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Beltran H;Tomlins S;Aparicio A;Arora V;Rickman D;Ayala G;Huang J;True L;Gleave ME;Soule H;Logothetis C;Rubin MA
通讯作者：
Rubin MA
影响因子：
158.5
作者：
Chi, Kim N.;Agarwal, Neeraj;Chowdhury, Simon
通讯作者：
Chowdhury, Simon