PP121在原发性和转移性非小细胞肺癌中的疗效。

IF 2.3 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Quincy A Quick
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引用次数: 2

摘要

酪氨酸激酶抑制剂是非小细胞肺癌(nsclc)的临床标准治疗选择,非小细胞肺癌是美国癌症相关死亡的主要原因。这些靶向药物包括第一代、第二代和第三代酪氨酸激酶抑制剂;然而,由于固有和获得性耐药,这些药物在治疗非小细胞肺癌方面缺乏临床疗效。这种抗性可能是不同途径的致癌信号介质遗传畸变的结果。本研究旨在探讨一种新的双酪氨酸激酶和PI3K抑制剂PP121作为非小细胞肺癌细胞系的靶向药物。本研究将PP121与健康人星形胶质细胞共培养,星形胶质细胞是位于非小细胞肺癌脑转移灶脑中的一种常见细胞类型。迄今为止,很少有临床前研究检测PP121作为抗癌药物的疗效,据我所知,之前没有研究评估其在治疗非小细胞肺癌中的治疗潜力。为了研究非小细胞肺癌的临床异质性,我们使用了患者源性腺癌(ADC)和鳞状细胞癌(SCC)异种移植模型,它们表现出表皮生长因子受体(EGFR)突变和间充质上皮转化因子(MET)扩增。值得注意的是,EGFR和MET都是已知的酪氨酸激酶抑制剂耐药性的贡献者;因此,上述突变和扩增使得PP121在这些实体瘤中的作用得以评估。此外,采用非小细胞肺癌细胞和星形胶质细胞共培养的模型系统来评估PP121在多细胞环境下对ADC和SCC细胞侵袭的影响。本研究结果表明,PP121通过下调药效学靶点在上述模型系统中发挥抗肿瘤作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Efficacy of PP121 in primary and metastatic non‑small cell lung cancers.

Efficacy of PP121 in primary and metastatic non‑small cell lung cancers.

Efficacy of PP121 in primary and metastatic non‑small cell lung cancers.

Efficacy of PP121 in primary and metastatic non‑small cell lung cancers.

Tyrosine kinase inhibitors are a clinically standard treatment option for non-small cell lung cancers (NSCLCs), the leading cause of cancer-related deaths in the US. These targeted agents include first, second and third generation tyrosine kinase inhibitors; however, these lack clinical efficacy in the treatment of NSCLC due to intrinsic and acquired resistance. This resistance may be a result of genetic aberrations in oncogenic signaling mediators of divergent pathways. The present study aimed to investigate a novel dual tyrosine kinase and PI3K inhibitor, PP121, as a targeted agent in NSCLC cell lines. The present study co-cultured PP121 with healthy human astrocytes, a prevalent cell type located in the brain of NSCLC brain metastases. To date, few preclinical studies have examined the efficacy of PP121 as an anticancer agent, and to the best of my knowledge, no previous studies have previously evaluated its therapeutic potential in the treatment of NSCLC. To investigate the clinical heterogeneity of NSCLC, patient-derived adenocarcinoma (ADC) and squamous cell carcinoma (SCC) xenograft models were used, which exhibited epidermal growth factor receptor (EGFR) mutations and mesenchymal-epithelial transition (MET) factor amplifications. Notably, both EGFR and MET are known contributors to tyrosine kinase inhibitor resistance; thus, the aforementioned mutations and amplifications enabled the effects of PP121 to be evaluated in these solid tumors. In addition, a co-cultured model system using both NSCLC cells and astrocytes was employed to assess the effects of PP121 on the invasion of ADC and SCC cells in a multicellular environment. Results of the present study demonstrated that PP121 exerted an antitumorigenic effect in the aforementioned model systems via downregulation of pharmacodynamic targets.

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来源期刊
Biomedical reports
Biomedical reports MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
4.10
自引率
0.00%
发文量
86
期刊介绍: Biomedical Reports is a monthly, peer-reviewed journal, dedicated to publishing research across all fields of biology and medicine, including pharmacology, pathology, gene therapy, genetics, microbiology, neurosciences, infectious diseases, molecular cardiology and molecular surgery. The journal provides a home for original research, case reports and review articles.
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