Adaptation to Hypoxia May Promote Therapeutic Resistance to Androgen Receptor Inhibition in Triple-Negative Breast Cancer.
Adaptation to Hypoxia May Promote Therapeutic Resistance to Androgen Receptor Inhibition in Triple-Negative Breast Cancer.
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DOI：
10.3390/ijms23168844
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发表时间：
2022-08-09
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
Triple-negative breast cancer (TNBC) surpasses other BC subtypes as the most challenging to treat due to its lack of traditional BC biomarkers. Nearly 30% of TNBC patients express the androgen receptor (AR), and the blockade of androgen production and AR signaling have been the cornerstones of therapies for AR-positive TNBC. However, the majority of women are resistant to AR-targeted therapy, which is a major impediment to improving outcomes for the AR-positive TNBC subpopulation. The hypoxia signaling cascade is frequently activated in the tumor microenvironment in response to low oxygen levels; activation of the hypoxia signaling cascade allows tumors to survive despite hypoxia-mediated interference with cellular metabolism. The activation of hypoxia signaling networks in TNBC promotes resistance to most anticancer drugs including AR inhibitors. The activation of hypoxia network signaling occurs more frequently in TNBC compared to other BC subtypes. Herein, we examine the (1) interplay between hypoxia signaling networks and AR and (2) whether hypoxia and hypoxic stress adaptive pathways promote the emergence of resistance to therapies that target AR. We also pose the well-supported question, “Can the efficacy of androgen-/AR-targeted treatments be enhanced by co-targeting hypoxia?” By critically examining the evidence and the complex entwinement of these two oncogenic pathways, we argue that the simultaneous targeting of androgen biosynthesis/AR signaling and hypoxia may enhance the sensitivity of AR-positive TNBCs to AR-targeted treatments, derail the emergence of therapy resistance, and improve patient outcomes.
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影响因子：
9
作者：
Chen T;Liu R;Niu Y;Mo H;Wang H;Lu Y;Wang L;Sun L;Wang Y;Tu K;Liu Q
通讯作者：
Liu Q
DOI：
10.1016/j.neo.2022.01.003
发表时间：
2022-03
期刊：
Neoplasia (New York, N.Y.)
影响因子：
--
作者：
Carroll CP;Bolland H;Vancauwenberghe E;Collier P;Ritchie AA;Clarke PA;Grabowska AM;Harris AL;McIntyre A
通讯作者：
McIntyre A
影响因子：
8
作者：
Chen, Anna;Sceneay, Jaclyn;Moller, Andreas
通讯作者：
Moller, Andreas
影响因子：
--
作者：
Bharti, Santosh K;Mironchik, Yelena;Bhujwalla, Zaver M
通讯作者：
Bhujwalla, Zaver M
影响因子：
11.4
作者：
Delgado-Martin C;Meyer LK;Huang BJ;Shimano KA;Zinter MS;Nguyen JV;Smith GA;Taunton J;Winter SS;Roderick JR;Kelliher MA;Horton TM;Wood BL;Teachey DT;Hermiston ML
通讯作者：
Hermiston ML