Efficacy of PARP inhibition combined with EZH2 inhibition depends on BRCA mutation status and microenvironment in breast cancer.
Efficacy of PARP inhibition combined with EZH2 inhibition depends on BRCA mutation status and microenvironment in breast cancer.
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DOI：
10.1111/febs.15730
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Chen MK
中科院分区：
文献类型：
--
作者：
Chen MK
PARP 抑制剂 (PARPi) 和 EZH2 抑制剂联合使用的功效已在具有 BRCA1 突变或 BRCA2 突变的乳腺癌细胞中进行了研究。然而，早期的研究重点是这种组合对 BRCA 突变乳腺癌的疗效，而不是对 BRCA 成熟乳腺癌的疗效。杨等人。观察到 PARP1 缺失与 PRC2 缺失联合 EZH2 缺失并不影响体外 BRCA1/2 野生型乳腺癌细胞的生长。此外，杨等人。报道称，这种组合通过调节肿瘤微环境诱导 M2 型巨噬细胞的血管生成和分化，刺激体内 BRCA1/2 熟练乳腺癌细胞的合成活力。杨等人的研究结果。提供的证据表明，在 PARPi 联合疗法的研究中应采用体外和动物模型，以便在这些研究中涉及肿瘤微环境的改变。这些 PARP 抑制与 EZH2 抑制联合治疗乳腺癌的研究表明，这种组合可能有益于携带 BRCA1 突变肿瘤的乳腺癌患者，但该组合也可能会增强 BRCA2 突变肿瘤的复发，甚至可能促进 BRCA 成熟的癌细胞存活。因此，未来临床试验中应根据BRCA1突变状态来选择接受PARPi和EZH2抑制剂联合治疗的乳腺癌患者。
The efficacy of the combination of a PARP inhibitor (PARPi) and an EZH2 inhibitor has been investigated in breast cancer cells with either BRCA1 mutation or BRCA2 mutation. However, earlier studies focused on the efficacy of this combination against BRCA-mutated but not BRCA-proficient breast cancer. Yang et al. observed that PARP1 depletion combined with EZH2 depletion via PRC2 depletion did not affect the growth of BRCA1/2 wild-type breast cancer cells in vitro. Moreover, Yang et al. reported that this combination stimulated synthetic viability of BRCA1/2-proficient breast cancer cells in vivo by regulating the tumor microenvironment to induce angiogenesis and differentiation of M2-type macrophages. The findings of Yang et al. provided evidence that both in vitro and animal models should be employed in the studies of PARPi combination therapies in order to involve the alteration of the tumor microenvironment in these investigations. These studies of PARP inhibition combined with EZH2 inhibition in breast cancer showed that this combination may benefit breast cancer patients carrying BRCA1-mutated tumor, but the combination may also enhance recurrence of BRCA2-mutated tumor and may even promote BRCA-proficient cancer cell survival. Therefore, BRCA1 mutation status should be used to select breast cancer patients for PARPi and EZH2 inhibitor combination treatment in clinical trials in the future.
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影响因子：
--
作者：
Caruso LB;Martin KA;Lauretti E;Hulse M;Siciliano M;Lupey-Green LN;Abraham A;Skorski T;Tempera I
通讯作者：
Tempera I
影响因子：
17.1
作者：
Pommier, Yves;O'Connor, Mark J.;de Bono, Johann
通讯作者：
de Bono, Johann
影响因子：
21.3
作者：
Rondinelli, Beatrice;Gogola, Ewa;D'Andrea, Alan D.
通讯作者：
D'Andrea, Alan D.
影响因子：
5.2
作者：
Martin CJ;Moorehead RA
通讯作者：
Moorehead RA
影响因子：
50.5
作者：
Tobalina, L.;Armenia, J.;Forment, J., V
通讯作者：
Forment, J., V