Trastuzumab emtansine suppresses the growth of HER2-positive small-cell lung cancer in preclinical models

Morimura, Osamu; Minami, Toshiyuki; Kijima, Takashi; Koyama, Shohei; Otsuka, Tomoyuki; Kinehara, Yuhei; Osa, Akio; Higashiguchi, Masayoshi; Miyake, Kotaro; Nagatomo, Izumi; Hirata, Haruhiko; Iwahori, Kota; Takimoto, Takayuki; Takeda, Yoshito; Kida, Hiroshi; Kumanogoh, Atsushi

doi:10.1016/j.bbrc.2017.05.090

Cited by 9 publications

(6 citation statements)

References 20 publications

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“…It binds to the extracellular domain of the HER2/neu receptor, inhibits downstream signaling and activates immune mechanisms that ultimately contribute to its antitumor effect [13]. HER2 is overexpressed in a variety of carcinomas, like breast, ovarian, lung, and gastric tumors [14,15]. Among them, trastuzumab administration is allowed to treat HER2-positive metastatic breast cancers and HER2-positive stomach tumors and it has transformed the complicated prognosis of these subtypes of carcinomas [16].…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel-Trastuzumab Mixed Nanovehicle to Target HER2-Overexpressing Tumors

et al. 2019

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Paclitaxel is one of the most widely used chemotherapeutic agents thanks to its effectiveness and broad spectrum of antitumor activity. However, it has a very poor aqueous solubility and a limited specificity. To solve these handicaps, a novel paclitaxel-trastuzumab targeted transport nanosystem has been developed and characterized in this work to specifically treat cancer cells that overexpress the human epidermal growth factor receptor-2 (HER2). Methods: Alginate and piperazine nanoparticles were synthetized and conjugated with paclitaxel:β-cyclodextrins complexes and trastuzumab. Conjugated nanoparticles (300 nm) were characterized and their internalization in HER2-overexpressing tumor cells was analyzed by immunofluorescence. Its specific antitumor activity was studied in vitro using human cell lines with different levels of HER2-expression. Results: In comparison with free paclitaxel:β-cyclodextrins complexes, the developed conjugated nanovehicle presented specificity for the treatment of HER2-overpressing cells, in which it was internalized by endocytosis. Conclusions: It seems that potentially avoiding the conventional adverse effects of paclitaxel treatment could be possible with the use of the proposed mixed nanovehicle, which improves its bioavailability and targets HER2-positive cancer cells.

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Section: Introductionmentioning

confidence: 99%

Paclitaxel-Trastuzumab Mixed Nanovehicle to Target HER2-Overexpressing Tumors

et al. 2019

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“…HER2 is a proto-oncogene which encodes a transmembrane glycoprotein, and its over-expression is involved in the regulation of abnormal proliferation, differentiation and anti-apoptotic processes [12][13]. The HER2 gene is over-expressed in many malignant tumors [14] and trastuzumab, which targets HER2, has been successfully used in the treatment of metastatic breast cancer with HER2-overexpression [15].There has been recent study on HER2 expression in ovarian cancer and its relationship with prognosis [16], and some researchers have found that HER2 gene expression has a key role in the occurrence and development of epithelial ovarian cancer; with the 5-year survival rate of patients with HER2 over-expression significantly decreased [17], suggesting it might be used as a poor prognostic factor. This supports our finding that HER2 expression in ovarian cancer tissues is significantly higher than in normal ovarian tissues and suggests it is involved in the cancer's occurrence and development.…”

Section: Discussionmentioning

confidence: 99%

Effects of trastuzumab on the proliferation and apoptosis of ovarian cancer cells

Cong

Liu

Hou

et al. 2019

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This study investigates the effects of trastuzumab on the proliferation and apoptosis of ovarian cancer cells. Epithelial ovarian cancer tissues were collected from 60 patients, benign ovarian tissues from 45 patients and normal ovarian tissues from 30 patients. Human epidermal growth factor receptor 2 (HER2) protein expression was measured by immunohistochemistry and mRNA expression by quantitative real-time polymerase chain reaction (RT-PCR). Proliferation and apoptosis of SKOV3 cells were then measured by MTS assay and flow cytometry and cleaved caspase-3 expression was detected by Western blot. Our results established that HER2 protein is expressed in tumor tissues, benign tissues and normal tissues and its positive expression rate in tumor tissues is significantly higher than in benign tissues and normal tissues (p<0.05). In addition, the relative HER2 mRNA expression in epithelial ovarian tumor tissues was 55 times higher than that in normal ovarian tissues (p<0.01). Our research confirmed that trastuzumab significantly inhibited SKOV3 cell proliferation and increased cell apoptosis and cleaved caspase-3 expression in the experimental group compared to controls (p<0.05). In conclusion, HER2 protein is over-expressed in epithelial ovarian cancer tissues, and trastuzumab exerts anti-tumor effect by inhibiting cell proliferation and inducing apoptosis, suggesting it might be a novel approach for the treatment of ovarian cancer.

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“…In preclinical studies, T-DM1 is demonstrated available in vitro growth suppression of HER2-mutation NSCLC cells [29]. Meanwhile, the vitro animal experimental data showed that T-DM1 inhibited the growth of SBC-3/SN-38 xenografts more obviously compared with trastuzumab, showing better potential against small cell lung cancer (SCLC) [30]. T-DM1 has also shown vital antitumor effects in clinical trials.…”

Section: T-dm1(trastuzumab-emtansin)mentioning

confidence: 99%

Progress in anti-HER2 targeted therapy of metastatic lung cancer

Xiao

Jia

2021

E3S Web Conf.

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Lung cancer is one of the most common malignant tumors in the world and one of the main causes of cancer death. In lung cancer, metastatic stage accounted for a large percentage. It is a global disease affecting human health, with high incidence rate, low malignant degree and other characteristics. After decades of exploration, anti-HER2 targeted therapy in breast has made breakthrough progress, obtained encouraging clinical efficacy, and fully improved the quality of the life of patients. Because of this, more and more researchers are focusing on anti-HER2 in metastatic lung cancer targeting research. For the past few years, new targeted drugs have been constantly developed for anti-HER2 in metastatic lung cancer, and promising data results have been obtained in clinical trials and cohort study. This article provides a review of the clinical research progress of anti-HER2 targeted therapy in metastatic lung cancer in recent years, with a view to further guiding clinical treatment and providing more treatment options for patients.

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Trastuzumab emtansine suppresses the growth of HER2-positive small-cell lung cancer in preclinical models

Cited by 9 publications

References 20 publications

Paclitaxel-Trastuzumab Mixed Nanovehicle to Target HER2-Overexpressing Tumors

Paclitaxel-Trastuzumab Mixed Nanovehicle to Target HER2-Overexpressing Tumors

Effects of trastuzumab on the proliferation and apoptosis of ovarian cancer cells

Progress in anti-HER2 targeted therapy of metastatic lung cancer

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