Phosphoinositide 3-Kinase Signaling in the Tumor Microenvironment: What Do We Need to Consider When Treating Chronic Lymphocytic Leukemia With PI3K Inhibitors?
Phosphoinositide 3-Kinase Signaling in the Tumor Microenvironment: What Do We Need to Consider When Treating Chronic Lymphocytic Leukemia With PI3K Inhibitors?
复制标题
肿瘤微环境中的磷酸肌醇3-激酶信号传导：在用PI3K抑制剂治疗慢性淋巴细胞性白血病时，我们需要考虑什么？
DOI：
10.3389/fimmu.2020.595818
复制
发表时间：
2020
影响因子：
7.3
通讯作者：
Roessner PM
中科院分区：
文献类型：
--
作者：
Aydin E;Faehling S;Saleh M;Llaó Cid L;Seiffert M;Roessner PM
磷脂酰肌醇3-激酶（PI 3 Ks）及其下游蛋白质构成参与正常细胞生长和细胞恶性转化的信号通路。在生理条件下，PI 3 K信号传导依赖于细胞外信号调节各种细胞功能，例如凋亡、存活、增殖和生长。癌基因或生长因子受体的突变损伤引起的这些细胞外信号的恶化可能会导致这种信号级联反应的过度激活，这被认为是癌症的标志。尽管PI 3 K通路的较高活化在许多类型的癌症中是常见的，但它首次在慢性淋巴细胞白血病（CLL）中被治疗靶向，证明了其在B细胞受体（BCR）信号传导和恶性B细胞扩增中的重要性。PI 3 K通路的生物活性不仅限于癌细胞，而且对肿瘤微环境的许多组分也至关重要，因为PI 3 K信号传导调节细胞因子反应，并确保免疫细胞的发育和功能。因此，PI 3 K抑制的成功或失败与微环境刺激密切相关。在这篇综述中，我们概述了PI 3 K抑制对肿瘤微环境的影响，特别关注CLL。承认基于PI 3 K受体的治疗对CLL中肿瘤微环境的影响可以作为改善药物开发的基本原理，解释治疗相关的不良事件，并提出CLL中的新组合治疗策略。
Phosphoinositide 3-kinases (PI3Ks) and their downstream proteins constitute a signaling pathway that is involved in both normal cell growth and malignant transformation of cells. Under physiological conditions, PI3K signaling regulates various cellular functions such as apoptosis, survival, proliferation, and growth, depending on the extracellular signals. A deterioration of these extracellular signals caused by mutational damage in oncogenes or growth factor receptors may result in hyperactivation of this signaling cascade, which is recognized as a hallmark of cancer. Although higher activation of PI3K pathway is common in many types of cancer, it has been therapeutically targeted for the first time in chronic lymphocytic leukemia (CLL), demonstrating its significance in B-cell receptor (BCR) signaling and malignant B-cell expansion. The biological activity of the PI3K pathway is not only limited to cancer cells but is also crucial for many components of the tumor microenvironment, as PI3K signaling regulates cytokine responses, and ensures the development and function of immune cells. Therefore, the success or failure of the PI3K inhibition is strongly related to microenvironmental stimuli. In this review, we outline the impacts of PI3K inhibition on the tumor microenvironment with a specific focus on CLL. Acknowledging the effects of PI3K inhibitor-based therapies on the tumor microenvironment in CLL can serve as a rationale for improved drug development, explain treatment-associated adverse events, and suggest novel combinatory treatment strategies in CLL.
登录
查看更多内容
影响因子：
11.2
作者：
Ahmad, Shamim;Abu-Eid, Rasha;Khleif, Samir N.
通讯作者：
Khleif, Samir N.
影响因子：
11.4
作者：
Bertrand, FE;Spengemen, JD;McCubrey, JA
通讯作者：
McCubrey, JA
影响因子：
7.3
作者：
Ciraolo E;Iezzi M;Marone R;Marengo S;Curcio C;Costa C;Azzolino O;Gonella C;Rubinetto C;Wu H;Dastrù W;Martin EL;Silengo L;Altruda F;Turco E;Lanzetti L;Musiani P;Rückle T;Rommel C;Backer JM;Forni G;Wymann MP;Hirsch E
通讯作者：
Hirsch E
影响因子：
4.4
作者：
Boyle, Keith B.;Gyori, David;Hawkins, Phillip T.
通讯作者：
Hawkins, Phillip T.
影响因子：
64.8
作者：
Ali K;Soond DR;Pineiro R;Hagemann T;Pearce W;Lim EL;Bouabe H;Scudamore CL;Hancox T;Maecker H;Friedman L;Turner M;Okkenhaug K;Vanhaesebroeck B
通讯作者：
Vanhaesebroeck B