RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer.
RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer.
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对于ER阴性的绝经后乳腺癌，RANK是一个预后不良的指标和治疗的新靶点。
DOI：
10.15252/emmm.202216715
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发表时间：
2023-04-11
影响因子：
11.1
通讯作者：
Gonzalez-Suarez, Eva
中科院分区：
文献类型：
--
作者：
Ciscar, Marina;Trinidad, Eva M.;Perez-Chacon, Gema;Alsaleem, Mansour;Jimenez, Maria;Jimenez-Santos, Maria J.;Perez-Montoyo, Hector;Sanz-Moreno, Adrian;Vethencourt, Andrea;Toss, Michael;Petit, Anna;Soler-Monso, Maria T.;Lopez, Victor;Gomez-Miragaya, Jorge;Gomez-Aleza, Clara;Dobrolecki, Lacey E.;Lewis, Michael T.;Bruna, Alejandra;Mouron, Silvana;Quintela-Fandino, Miguel;Al-Shahrour, Fatima;Martinez-Aranda, Antonio;Sierra, Angels;Green, Andrew R.;Rakha, Emad;Gonzalez-Suarez, Eva
关键词：
Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor, denosumab, in breast cancer patients, beyond the bone, is unclear. Aiming to select patients who may benefit from denosumab, we hereby analyzed RANK and RANKL protein expression in more than 2,000 breast tumors (777 estrogen receptor‐negative, ER−) from four independent cohorts. RANK protein expression was more frequent in ER− tumors, where it associated with poor outcome and poor response to chemotherapy. In ER− breast cancer patient‐derived orthoxenografts (PDXs), RANKL inhibition reduced tumor cell proliferation and stemness, regulated tumor immunity and metabolism, and improved response to chemotherapy. Intriguingly, tumor RANK protein expression associated with poor prognosis in postmenopausal breast cancer patients, activation of NFKB signaling, and modulation of immune and metabolic pathways, suggesting that RANK signaling increases after menopause. Our results demonstrate that RANK protein expression is an independent biomarker of poor prognosis in postmenopausal and ER− breast cancer patients and support the therapeutic benefit of RANK pathway inhibitors, such as denosumab, in breast cancer patients with RANK+ ER− tumors after menopause. The analyses of RANK and RANKL expression in large cohorts of breast cancer samples and functional studies in RANK+ breast cancer patient‐derived xenografts (PDXs) revealed a key role for RANK in postmenopausal women with estrogen receptor negative ER‐ breast cancer.
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影响因子：
11.8
作者：
Benítez S;Cordero A;Santamaría PG;Redondo-Pedraza J;Rocha AS;Collado-Solé A;Jimenez M;Sanz-Moreno A;Yoldi G;Santos JC;De Benedictis I;Gómez-Aleza C;Da Silva-Álvarez S;Troulé K;Gómez-López G;Alcazar N;Palmero I;Collado M;Serrano M;Gonzalez-Suarez E
通讯作者：
Gonzalez-Suarez E
影响因子：
--
作者：
Martínez-Aranda A;Hernández V;Guney E;Muixí L;Foj R;Baixeras N;Cuadras D;Moreno V;Urruticoechea A;Gil M;Oliva B;Moreno F;González-Suarez E;Vidal N;Andreu X;Seguí MA;Ballester R;Castella E;Sierra A
通讯作者：
Sierra A
影响因子：
2.2
作者：
Miyazaki T;Tokimura F;Tanaka S
通讯作者：
Tanaka S
影响因子：
16.6
作者：
Gómez-Aleza C;Nguyen B;Yoldi G;Ciscar M;Barranco A;Hernández-Jiménez E;Maetens M;Salgado R;Zafeiroglou M;Pellegrini P;Venet D;Garaud S;Trinidad EM;Benítez S;Vuylsteke P;Polastro L;Wildiers H;Simon P;Lindeman G;Larsimont D;Van den Eynden G;Velghe C;Rothé F;Willard-Gallo K;Michiels S;Muñoz P;Walzer T;Planelles L;Penninger J;Azim HA Jr;Loi S;Piccart M;Sotiriou C;González-Suárez E
通讯作者：
González-Suárez E
影响因子：
51.1
作者：
Coleman, Robert;Finkelstein, Dianne M.;Chan, Arlene
通讯作者：
Chan, Arlene