Regulation of pancreatic cancer therapy resistance by chemokines.
Regulation of pancreatic cancer therapy resistance by chemokines.
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DOI：
10.1016/j.semcancer.2022.08.010
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发表时间：
2022-11
影响因子：
14.5
通讯作者：
Jain, Maneesh
中科院分区：
文献类型：
--
作者：
Gautam, Shailendra K.;Basu, Soumi;Aithal, Abhijit;Dwivedi, Nidhi ., V;Gulati, Mansi;Jain, Maneesh
关键词：
胰腺导管腺癌（Pancreatic ductal adencarcinoma， PDAC）是一种高致死性恶性肿瘤，其特点是对化疗具有高耐药性和低反应。此外，免疫原性差的胰腺肿瘤构成免疫抑制肿瘤微环境（TME），使得基于免疫治疗的方法无效。了解治疗耐药的机制，确定新的靶点，并制定有效的策略来克服耐药可以显著影响PDAC患者的管理。趋化因子是一种小的可溶性因子，在PDAC发病过程中显著失调，有助于肿瘤生长、转移、免疫细胞运输和治疗抵抗。到目前为止，已经探索了不同的趋化因子途径作为PDAC的治疗靶点，并在最近的临床试验中取得了一些有希望的结果。特别是，免疫疗法，如免疫检查点阻断疗法和CAR-T细胞疗法，在与趋化因子靶向治疗相结合时显示出有希望的结果。考虑到趋化因子在PDAC中的新出现的病理和临床意义，我们回顾了导致PDAC耐药的主要趋化因子调控途径以及正在进行的针对趋化因子信号传导的努力。本文讨论了趋化因子在调节PDAC耐药中的作用，并强调了针对趋化因子调节途径的持续努力，以提高各种治疗方式的疗效。
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by high resistance and poor response to chemotherapy. In addition, the poorly immunogenic pancreatic tumors constitute an immunosuppressive tumor microenvironment (TME), that render immunotherapy-based approaches ineffective. Understanding the mechanisms of therapy resistance, identifying new targets, and developing effective strategies to overcome resistance can significantly impact the management of PDAC patients. Chemokines are small soluble factors that are significantly deregulated during PDAC pathogenesis, contributing to tumor growth, metastasis, immune cell trafficking, and therapy resistance. Thus far, different chemokine pathways have been explored as therapeutic targets in PDAC, with some promising results in recent clinical trials. Particularly, immunotherapies such as immune check point blockade therapies and CAR-T cell therapies have shown promising results when combined with chemokine targeted therapies. Considering the emerging pathological and clinical significance of chemokines in PDAC, we reviewed major chemokine-regulated pathways leading to therapy resistance and the ongoing endeavors to target chemokine signaling in PDAC. This review discusses the role of chemokines in regulating therapy resistance in PDAC and highlights the continuing efforts to target chemokine-regulated pathways to improve the efficacy of various treatment modalities.
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DOI：
10.1158/1078-0432.ccr-21-1681
发表时间：
2021-12-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
通讯作者：
--
影响因子：
50.3
作者：
Bear AS;Vonderheide RH;O'Hara MH
通讯作者：
O'Hara MH
影响因子：
4.3
作者：
Estrada-Bernal, Adriana;Chatterjee, Moumita;Williams, Terence M.
通讯作者：
Williams, Terence M.
影响因子：
9
作者：
Cameron, JL;Riall, TS;Belcher, KA
通讯作者：
Belcher, KA
DOI：
10.1073/pnas.1320318110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Feig, Christine;Jones, James O.;Fearon, Douglas T.
通讯作者：
Fearon, Douglas T.