The Effects of Chemotherapeutics on the Ovarian Cancer Microenvironment.
The Effects of Chemotherapeutics on the Ovarian Cancer Microenvironment.
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化疗药物对卵巢癌微环境的影响。
DOI：
10.3390/cancers13133136
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发表时间：
2021-06-23
期刊：
影响因子：
5.2
通讯作者：
Lengyel E
中科院分区：
文献类型：
--
作者：
Eckert MA;Orozco C;Xiao J;Javellana M;Lengyel E
癌细胞是大多数批准的疗法的目标。越来越多的证据表明，这些药物在调节宿主细胞的生物学及其与癌细胞（包括血管、成纤维细胞、免疫细胞和脂肪细胞等）的相互作用方面具有重要作用。本文综述了常用治疗药物在肿瘤微环境中的潜在作用，重点是癌症相关的成纤维细胞。这包括强调常用于治疗高级别浆液性卵巢癌的疗法（例如，铂、紫杉烷、PARP抑制剂和抗血管生成剂）。包括体外，体内和临床研究，并提供关于如何最好地解释治疗对正常细胞的影响的观点。高级别浆液性卵巢癌（HGSOC）的特征在于由癌症相关成纤维细胞（CAF）、免疫细胞、内皮细胞和脂肪细胞组成的复杂且动态的肿瘤微环境（TME）。虽然大多数批准的疗法靶向癌细胞，但越来越多的证据表明，化疗药物在调节组成TME的各种细胞的生物学方面具有重要作用。了解非转化细胞如何响应和适应已建立的治疗方法是完全理解其作用并开发中断不希望的肿瘤-基质相互作用的新疗法所必需的。在这里，我们回顾了化疗药物对宿主来源的TME的正常细胞成分的影响，重点是CAFs。我们专注于用于治疗HGSOC的疗法，并综合关注其他癌症类型和良性组织的研究结果。诸如铂衍生物、紫杉烷和PARP抑制剂的药剂广泛地影响TME，并通过改变肿瘤器官中肿瘤和基质细胞之间的双向串扰来促进或抑制CAF的促肿瘤发生作用。虽然大多数化疗研究集中在癌细胞，但这些研究强调在评估化疗药物时需要考虑肿瘤器官内的所有细胞类型。
Cancer cells are the target of most approved therapies. A growing body of evidence suggests that these agents have important roles in modulating the biology of host cells and their interactions with cancer cells, including blood vessels, fibroblasts, immune and fat cells, among others. This review provides an overview of potential roles of commonly used therapeutics in the tumor microenvironment, with a focus on cancer-associated fibroblasts. This includes an emphasis on therapies commonly used for the treatment of high-grade serous ovarian cancers (e.g., platinum, taxanes, PARP inhibitors, and anti-angiogenic agents). In vitro, in vivo, and clinical studies are included, and perspectives offered on how to best interpret the influence of therapeutics on normal cells. High-grade serous ovarian cancer (HGSOC) is characterized by a complex and dynamic tumor microenvironment (TME) composed of cancer-associated fibroblasts (CAFs), immune cells, endothelial cells, and adipocytes. Although most approved therapies target cancer cells, a growing body of evidence suggests that chemotherapeutic agents have an important role in regulating the biology of the diverse cells that compose the TME. Understanding how non-transformed cells respond and adapt to established therapeutics is necessary to completely comprehend their action and develop novel therapeutics that interrupt undesired tumor–stroma interactions. Here, we review the effects of chemotherapeutic agents on normal cellular components of the host-derived TME focusing on CAFs. We concentrate on therapies used in the treatment of HGSOC and synthesize findings from studies focusing on other cancer types and benign tissues. Agents such as platinum derivatives, taxanes, and PARP inhibitors broadly affect the TME and promote or inhibit the pro-tumorigenic roles of CAFs by modifying the bidirectional cross-talk between tumor and stromal cells in the tumor organ. While most chemotherapy research focuses on cancer cells, these studies emphasize the need to consider all cell types within the tumor organ when evaluating chemotherapeutics.
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影响因子：
28.2
作者：
Eckert MA;Pan S;Hernandez KM;Loth RM;Andrade J;Volchenboum SL;Faber P;Montag A;Lastra R;Peter ME;Yamada SD;Lengyel E
通讯作者：
Lengyel E
DOI：
10.1158/1078-0432.ccr-09-0311
发表时间：
2009-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Blair BG;Larson CA;Safaei R;Howell SB
通讯作者：
Howell SB
影响因子：
22.7
作者：
Ali, H. Raza;Jackson, Hartland W.;Bodenmiller, Bernd
通讯作者：
Bodenmiller, Bernd
影响因子：
9
作者：
Che Y;Wang J;Li Y;Lu Z;Huang J;Sun S;Mao S;Lei Y;Zang R;Sun N;He J
通讯作者：
He J
DOI：
10.1038/nrm.2017.53
发表时间：
2017-10
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Ray Chaudhuri A;Nussenzweig A
通讯作者：
Nussenzweig A