MESFER AL SHAHRANI, REEM GAHTANI, MOHAMMAD ABOHASSAN, MOHAMMAD ALSHAHRANI, YASSER ALRAEY, AYED DERA, MOHAMMAD RAJEH ASIRI, PRASANNA RAJAGOPALAN^*

Oncology Research, Vol.32, No.2, pp. 251-259, 2024, DOI:10.32604/or.2023.043139

Abstract Gastric cancers are caused primarily due to the activation and amplification of the EGFR or HER2 kinases resulting in cell proliferation, adhesion, angiogenesis, and metastasis. Conventional therapies are ineffective due to the intra-tumoral heterogeneity and concomitant genetic mutations. Hence, dual inhibition strategies are recommended to increase potency and reduce cytotoxicity. In this study, we have conducted computational high-throughput screening of the ChemBridge library followed by in vitro assays and identified novel selective inhibitors that have a dual impediment of EGFR/HER2 kinase activities. Diversity-based High-throughput Virtual Screening (D-HTVS) was used to screen the whole ChemBridge small molecular library against EGFR and… More > Graphic Abstract

DONGYANG WANG, YI CHEN, JING HUANG, YOU ZHANG, CHONGKUI SUN, YINGQIANG SHEN^*

BIOCELL, Vol.47, No.2, pp. 329-338, 2023, DOI:10.32604/biocell.2023.023489

Abstract Glucocorticoids (GC) are widely used to counter the adverse events during cancer therapy; nonetheless, previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells, especially in epidermal growth factor receptor (EGFR)-targeted therapy of head and neck squamous cell carcinoma (HNSCC) remaining to be elucidated. The primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying mechanism. HNSCC cell lines (HSC-3, SCC-25, SCC-9, and H-400) and the human oral keratinocyte (HOK) cell lines were assessed for GC receptor (GR) expression. The promoting tumor growth effect of… More >

Li Xu, Kang Li, Jia Li, Liyu Liu, Fang Xu, Yan Xu, Yi Kong, Xingxiang Pu, Qianzhi Wang, Jingyi Wang, Bolin Chen^*, Lin Wu^*

Oncologie, Vol.24, No.3, pp. 579-590, 2022, DOI:10.32604/oncologie.2022.022121

Abstract Background: Non-small cell lung cancer (NSCLC), caused by abnormal gene drive, may have primary drug resistance after treatment with tyrosine kinase inhibitors (EGFR-TKIs). Therefore, we explore whether the primary drug-resistant NSCLC treated with EGFR-TKI is related to the miR-21/Sonic Hedgehog (SHH)/PI3K/AKT pathway. Methods: The patients from our hospital who meet the AJCC TNM staging (7th edition) stage IIIB and stage IV NSCLC were selected in this case study. Thereafter, the treatment response of EGFR-TKIs was evaluated according to the solid tumor efficacy evaluation standard (version 1.1). The patients were divided into the EGFR-TKIs primary drug resistance group (EGFR-TKIs-Primary-R) and the… More >

Xinwen Wang, Fupeng Zhang, Xi Yang, Meiping Xue, Xiaoli Li, Yu Gao, Likun Liu

Oncology Research, Vol.27, No.8, pp. 871-877, 2019, DOI:10.3727/096504018X15426271404407

Abstract Second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), afatinib, has been approved for treating EGFR mutant lung cancer patients, but the mechanism of acquired resistance to afatinib has not been well studied. In this study, we established afatinib acquired resistant cell lines. Gene array technology was used to screen changes in gene expression between afatinib-resistant lung cancer cells and parental cells. Our results showed that secreted phosphoprotein 1 (SPP1) was significantly increased in afatinib-resistant lung cancer cells. To study the effect of SPP1 on afatinib resistance, siSPP1 was used to knock down SSP1 in afatinib-resistant lung cancer… More >

Youwei Zhang^*, Bi Chen^†, Yongsheng Wang^‡, Qi Zhao^‡, Weijun Wu^§, Peiying Zhang^*, Liyun Miao^‡, Sanyuan Sun^*

Oncology Research, Vol.27, No.7, pp. 751-761, 2019, DOI:10.3727/096504018X15372657298381

Abstract Acquired resistance remains a key challenge in epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) therapy in lung adenocarcinoma (LUAD). Recent studies have shown that Notch signaling is associated with drug resistance. However, its role and possible mechanisms in EGFR-TKI resistance are not yet clear. In our study, we found that among four members of NOTCH1–4, only NOTCH3 was upregulated in LUAD tissues and TKI-resistant cell line (HCC827GR6). Knockdown of NOTCH3 by siRNA significantly inhibited proliferative ability, and decreased colony and sphere formation in HCC827GR6 cells. Then miR-150 was identified as a posttranscriptional regulator of NOTCH3. Its expression was downregulated… More >

Jianping Xu, Xiaoyan Liu, Sheng Yang, Yuankai Shi

Oncology Research, Vol.28, No.2, pp. 127-133, 2020, DOI:10.3727/096504019X15707896762251

Abstract Apatinib, an oral small molecular receptor tyrosine kinase inhibitor (TKI) developed first in China, exerts antiangiogenic and antineoplastic function through selectively binding and inhibiting vascular endothelial growth factor receptor 2 (VEGFR-2). In this study, we aimed to explore the efficacy and safety profile of apatinib monotherapy, or combined with chemotherapy or endothelial growth factor receptor (EGFR)-TKI in heavily pretreated non-small cell lung cancer (NSCLC) patients with brain metastases. We performed a retrospective analysis for relapsed NSCLC patients with brain metastases from our institute, who received apatinib (250 mg or 500 mg p.o. qd) monotherapy, or combination with EGFR-TKI or chemotherapy… More >

Linn Woelber^*1, Sabrina Mathey^*1, Katharina Prieske^*†, Sascha Kuerti^*, Christoph Hillen^*, Eike Burandt^‡, Anja Coym^§, Volkmar Mueller^*, Barbara Schmalfeldt^*, Anna Jaeger^*

Oncology Research, Vol.28, No.6, pp. 645-659, 2020, DOI:10.3727/096504020X16076861118243

Abstract Therapeutic options in recurrent or metastasized vulvar squamous cell cancer (VSCC) not amenable to radiotherapy or radical surgery are limited. Evidence for the use of targeted therapies is sparse. All patients with VSCC treated at the Gynecological Cancer Center Hamburg-Eppendorf 2013–2019 were retrospectively evaluated for targeted therapeutic approaches. Furthermore, a MEDLINE, EMBASE, Web of Science, Scopus, and OVID database search was performed using the terms: “vulvar cancer” AND “targeted therapy,” “erlotinib,” “EGFR,” “bevacizumab,” “VEGF,” “pembrolizumab,” or “immunotherapy.” Twelve of 291 patients (4.1%) with VSCC received at least one targeted therapy at our institution. Previously, one or more platinumbased chemotherapy was… More >

Ching-Wen Huang^*, Cheng-Jen Ma^*†, Wei-Chih Su^*, Yi-Ting Chen^‡§, Hsiang-Lin Tsai^*¶, Yung-Sung Yeh^*#, Tsung-Kun Chang^*, Wen-Hung Hsu^**††, Fang-Jung Yu^**††, Jaw-Yuan Wang^{*¶‡‡§§¶¶##}

Oncology Research, Vol.28, No.7-8, pp. 701-714, 2020, DOI:10.3727/096504020X15986099915822

Abstract This study evaluated the survival effects of metronomic maintenance therapy with oral fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy with oral capecitabine (daily dose of 850 mg/m2 , twice daily, on days 1–14 every 3 weeks for 6 months) on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through… More >

Yudie Yang^*1, Xia Zhang^†1, Yajie Gao^*, Yan Dong^*, Di Wang^*, Yanping Huang^*, Tianhao Qu^*, Buqun Fan^*, Qizheng Li^*, Chunxia Zhang^*, Xiaonan Cui^*, Bin Zhang^*

Oncology Research, Vol.29, No.1, pp. 63-74, 2021, DOI:10.3727/096504022X16462176651719

Abstract Lung cancer is a malignant tumor with high incidence and mortality across the world. The use of immune checkpoint inhibitors for lung cancer has improved the prognosis of some lung cancer patients to a greater extent and provided a new direction for the clinical treatment of lung cancer. Immunotherapy still has limitations in terms of its appropriate population and adverse reactions. Particularly for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation, there has been no major breakthrough in current immunotherapy. Whether immunotherapy can bring new benefits after drug resistance is induced by tyrosine kinase inhibitor-targeted… More >

DAN ZHANG¹, HAIJING LIU¹, ZHENNAN YI², YUANYUAN LU³, YANYAN CHEN⁴, WEIQIANG SU², HUIBING LIN², ZHIHUI ZHANG^5,*, WEI LEI^6,*

BIOCELL, Vol.45, No.3, pp. 617-625, 2021, DOI:10.32604/biocell.2021.012504

Abstract Chemotherapy drug resistance is the main cause leading to the relapse and metastasis of non-small cell lung cancer (NSCLC) patients. Our study aimed to investigate the mechanism of pemetrexed resistance in NSCLC. Firstly, the pemetrexed (PEM)-resistant PC-9 and A549 lung adenocarcinoma cell lines (PC-9/PEM and A549/PEM) were established. The expression of thymidylate synthase (TS) in PC-9/PEM, A549/PEM, A549, and PC-9 cells were analyzed by qRT-PCR and western blot. Then, cell viability, colony formation, migration, and invasion were performed on PEM-resistant cells transfected with TS siRNA. The role of EGFR in PEM resistance of PEM-resistant cells was investigated using EGFR siRNA.… More >