Protein Kinase C as a Therapeutic Target in Non-Small Cell Lung Cancer.
Protein Kinase C as a Therapeutic Target in Non-Small Cell Lung Cancer.
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DOI：
10.3390/ijms22115527
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发表时间：
2021-05-24
影响因子：
5.6
通讯作者：
Hannun YA
中科院分区：
文献类型：
--
作者：
Sadeghi MM;Salama MF;Hannun YA
驱动导向疗法彻底改变了癌症治疗，与传统化疗相比具有相似或更好的疗效，并显着提高了生活质量。尽管取得了重大进展，但靶向治疗仍受到耐药性的极大限制，几乎所有接受治疗的患者都会出现耐药性。因此，识别耐药性的分子调节剂引起了人们的极大兴趣。最近的研究表明蛋白激酶 C (PKC) 同工酶是非小细胞肺癌 (NSCLC) 耐药性的介质。重要的是，之前关于 PKC 的发现表明该酶家族与多种组织中的肿瘤促进和肿瘤抑制生物学有关。在这里，我们通过对基于细胞系的研究的广泛分析来回顾 PKC 同工酶在 NSCLC 中的生物学作用，以更好地了解 PKC 抑制的基本原理。据报道，肺癌中 PKC 亚型 α、ε、η、ι、ze 上调，过度表达与 NSCLC 患者较差的预后相关。最重要的是，PKC 同工酶已被确定为 NSCLC 中酪氨酸激酶抑制剂耐药性的介质。然而不幸的是，PKC 导向的治疗方法并没有取得令人满意的结果，这可能是由于缺乏对 PKC 的具体评估。为了在临床试验中获得满意的结果，必须在患者入组之前建立并筛选 PKC 活性的预测生物标志物。此外，PKC 和分子驱动因素的串联抑制可能是防止 NSCLC 出现耐药性的潜在治疗策略。
Driver-directed therapeutics have revolutionized cancer treatment, presenting similar or better efficacy compared to traditional chemotherapy and substantially improving quality of life. Despite significant advances, targeted therapy is greatly limited by resistance acquisition, which emerges in nearly all patients receiving treatment. As a result, identifying the molecular modulators of resistance is of great interest. Recent work has implicated protein kinase C (PKC) isozymes as mediators of drug resistance in non-small cell lung cancer (NSCLC). Importantly, previous findings on PKC have implicated this family of enzymes in both tumor-promotive and tumor-suppressive biology in various tissues. Here, we review the biological role of PKC isozymes in NSCLC through extensive analysis of cell-line-based studies to better understand the rationale for PKC inhibition. PKC isoforms α, ε, η, ι, ζ upregulation has been reported in lung cancer, and overexpression correlates with worse prognosis in NSCLC patients. Most importantly, PKC isozymes have been established as mediators of resistance to tyrosine kinase inhibitors in NSCLC. Unfortunately, however, PKC-directed therapeutics have yielded unsatisfactory results, likely due to a lack of specific evaluation for PKC. To achieve satisfactory results in clinical trials, predictive biomarkers of PKC activity must be established and screened for prior to patient enrollment. Furthermore, tandem inhibition of PKC and molecular drivers may be a potential therapeutic strategy to prevent the emergence of resistance in NSCLC.
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影响因子：
56.9
作者：
COUSSENS, L;PARKER, PJ;ULLRICH, A
通讯作者：
ULLRICH, A
影响因子：
64.5
作者：
Antal CE;Hudson AM;Kang E;Zanca C;Wirth C;Stephenson NL;Trotter EW;Gallegos LL;Miller CJ;Furnari FB;Hunter T;Brognard J;Newton AC
通讯作者：
Newton AC
影响因子：
20.4
作者：
Chiappori, Alberto;Bepler, Gerold;von Pawel, Joachim
通讯作者：
von Pawel, Joachim
影响因子：
8
作者：
Caino, M. C.;Lopez-Haber, C.;Kazanietz, M. G.
通讯作者：
Kazanietz, M. G.
影响因子：
6.4
作者：
DALE, IL;GESCHER, A
通讯作者：
GESCHER, A