Phosphoinositide 3-Kinase Signaling Pathway in Pancreatic Ductal Adenocarcinoma Progression, Pathogenesis, and Therapeutics.
Phosphoinositide 3-Kinase Signaling Pathway in Pancreatic Ductal Adenocarcinoma Progression, Pathogenesis, and Therapeutics.
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DOI：
10.3389/fphys.2018.00335
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发表时间：
2018
影响因子：
4
通讯作者：
Singh PK
中科院分区：
文献类型：
--
作者：
Murthy D;Attri KS;Singh PK
胰腺导管腺癌（PDAC）是一种高度侵袭性的恶性肿瘤，其特点是发病突然、进展迅速、预后不良、治疗选择有限。早期胰腺病变中发现的关键信号通路的遗传改变对于胰腺上皮内肿瘤病变发展为浸润性癌至关重要。超过 90% 的 PDAC 肿瘤在 K-Ras 中存在驱动突变，可激活各种下游效应信号通路，包括磷酸肌醇 3 激酶 (PI3K) 通路。 PI3K 通路还对癌细胞表面存在的各种生长因子受体的刺激作出反应，进而调节下游信号级联。因此，肌醇信号传导充当复杂细胞信号传导网络的中心节点，影响癌细胞的生长、运动、代谢和存活。此外，最近的出版物强调了 PI3K 信号传导在基质细胞中的重要性，PI3K 信号传导通过改变肿瘤微环境来决定疾病结果。 PI3K 信号级联中突变的高发生率，伴随着平行信号通路的激活，使得 PI3K 成为药物治疗的有希望的候选者。在这篇综述中，我们描述了 PI3K 信号传导在胰腺癌发生和进展中的作用。我们还讨论了 PI3K 与其他主要细胞信号级联反应之间的串扰，以及针对胰腺导管腺癌的潜在治疗机会。
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by its sudden manifestation, rapid progression, poor prognosis, and limited therapeutic options. Genetic alterations in key signaling pathways found in early pancreatic lesions are pivotal for the development and progression of pancreatic intraepithelial neoplastic lesions into invasive carcinomas. More than 90% of PDAC tumors harbor driver mutations in K-Ras that activate various downstream effector-signaling pathways, including the phosphoinositide-3-kinase (PI3K) pathway. The PI3K pathway also responds to stimuli from various growth factor receptors present on the cancer cell surface that, in turn, modulate downstream signaling cascades. Thus, the inositide signaling acts as a central node in the complex cellular signaling networks to impact cancer cell growth, motility, metabolism, and survival. Also, recent publications highlight the importance of PI3K signaling in stromal cells, whereby PI3K signaling modifies the tumor microenvironment to dictate disease outcome. The high incidence of mutations in the PI3K signaling cascade, accompanied by activation of parallel signaling pathways, makes PI3K a promising candidate for drug therapy. In this review, we describe the role of PI3K signaling in pancreatic cancer development and progression. We also discuss the crosstalk between PI3K and other major cellular signaling cascades, and potential therapeutic opportunities for targeting pancreatic ductal adenocarcinoma.
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影响因子：
29.4
作者：
Apte MV;Wilson JS;Lugea A;Pandol SJ
通讯作者：
Pandol SJ
影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
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人类癌症中的磷酸肌醇3-激酶途径：遗传改变和治疗意义。
影响因子：
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作者：
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DOI：
10.1186/s13058-016-0740-2
发表时间：
2016-08-11
期刊：
Breast cancer research : BCR
影响因子：
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作者：
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通讯作者：
Marini FC
影响因子：
11.2
作者：
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