Pyrotinib: First Global Approval

Blair, Hannah A.

doi:10.1007/s40265-018-0997-0

Cited by 123 publications

(104 citation statements)

References 8 publications

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“…Tyrosine residues in the cytoplasmic domain of this receptor can be auto-phosphorylated by dimerization, resulting in activation of various signaling pathways related to cell proliferation and tumorigenesis [4]. Pyrotinib is an irreversible HER2 tyrosine kinase inhibitor that showed anti-tumor effect in breast cancer [8,9]. Clinical studies are underway to examine the anti-tumor effect of pyrotinib in gastric cancer [10] and lung cancer [11].…”

Section: Discussionmentioning

confidence: 99%

Radiosensitization of HER2-positive esophageal cancer cells by pyrotinib

et al. 2020

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Radiation therapy is a widely used treatment for esophageal cancer. However, radiation resistance might result in a poor prognosis. Overexpression of HER2 has been related to adaptive radiation resistance. Pyrotinib is a HER2 inhibitor that shows an anti-tumor effect in breast cancer. The present study aims to explore the influence of pyrotinib combined with radiotherapy on HER2-positive esophageal cancer cells and explore the underlying mechanism. We screened two cell lines (TE-1 and KYSE30) that highly express HER2 from several human esophageal cancer cell lines. Cells were treated with pyrotinib or/and radiation. Cell proliferation, cell cycle distribution, and cell migration were measured. The protein levels involved in cell cycle and DNA repair were measured by Western blot. Results showed that pyrotinib inhibited HER2 activation and exerted an anti-proliferative effect in TE-1 and KYSE30 cells. Furthermore, it enhanced the anti-proliferative effect of radiation in these two cell lines. These effects might be via inhibiting HER2 phosphorylation, inducing G0/G1 arrest, and reducing EMT and DNA repair. Our results indicated that pyrotinib sensitivitied HER2 positive esophageal cancer cells to radiation treatment through various mechanisms. These findings may provide a new therapeutic strategy for treating HER2 positive esophageal cancer.

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Section: Discussionmentioning

confidence: 99%

Radiosensitization of HER2-positive esophageal cancer cells by pyrotinib

et al. 2020

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“…Developing combination treatment of targeted therapies with cytotoxic agents is critical strategy for HER2 + breast cancer. Some studies showed that combination pyrotinib with capecitabine significantly improved PFS and ORR in patients with HER2 + metastatic breast cancer [11,12]. These results revealed the synergistic anticancer activities of pyrotinib plus capecitabine against HER2 + breast cancers.…”

Section: Introductionmentioning

confidence: 85%

Pyrotinib sensitizes 5‑fluorouracil‑resistant HER2-positive breast cancer cells to 5‑fluorouracil

Yi²,

Chen

et al. 2020

Preprint

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BACKGROUND: Clinical trials have shown that pyrotinib+ capecitabine significantly improved efficacy of patients with human epidermal growth factor receptor 2(HER2) +breast cancer. However, whether pyrotinib sensitizes 5‑Fluorouracil(5‑FU)‑resistant breast cancer cells to 5‑FU is unknown. This study aimed to investigate the effects of pyrotinib on HER2+breast cancer cells with resistance to 5‑FU and provide new clues for the pyrotinib treatment in 5-FU-resistant breast cancer.METHODS: the 5‑FU‑resistant breast cancer cell lines SK-BR-3/FU and MAD-MB-453/FU were established by continuous exposure of the parental cells to 5‑FU.The effects of pyrotinib on these cell lines were examined by growth inhibitory activity assay, reverse transcription‑quantitative polymerase chain reaction, Western blot analysis, high-performance liquid chromatography and animal experiments.RESULTS: Pyrotinib inhibited the proliferation of 5-FU-resistant and parental HER2-positive breast cancer cells and re-sensitized resistant cells to 5-FU by decreasing the expression of thymidylate synthase(TS) and ABC transporter subfamily G member 2(ABCG2). In a xenograft model, combination treatment with 5-FU and pyrotinib showed greater antitumor activity than either agent alone. CONCLUSIONS: Our results offer a preclinical rationale for clinical investigations of combination treatment with pyrotinib and 5-FU for 5-FU-resistant HER2-positive breast cancer.

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“…11 Pyrotinib is a pan-erbB/TKI inhibitor that can bind to and inhibit EGFR (ErbB1/HER1) and ErbB2/HER2 with a half maximal inhibitory concentration (IC50) of 5.6 and 8.1 nM, respectively. 12 China has recently approved the first global conditional use of pyrotinib in combination with capecitabine for the treatment of HER2-positive, advanced or metastatic breast cancer. 12 In addition, Phase I and Phase II development for use of pyrotinib in HER2-positive gastric cancer (GC) is underway in China and the USA.…”

Section: Introductionmentioning

confidence: 99%

“…12 China has recently approved the first global conditional use of pyrotinib in combination with capecitabine for the treatment of HER2-positive, advanced or metastatic breast cancer. 12 In addition, Phase I and Phase II development for use of pyrotinib in HER2-positive gastric cancer (GC) is underway in China and the USA. 13 Evaluation on the efficacy and safety of pyrotinib in other HER2-positive advanced solid tumors is also underway by some other studies (NCT02834936, NCT03480256, NCT02500199).…”

Section: Introductionmentioning

confidence: 99%

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<p>Pyrotinib treatment on HER2-positive gastric cancer cells promotes the released exosomes to enhance endothelial cell progression, which can be counteracted by apatinib</p>

Gao

Song

et al. 2019

OTT

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Aims: Pyrotinib is a newly developed irreversible pan-ErbB receptor tyrosine kinase inhibitor for treatment of human epidermal growth factor receptor 2 (HER2)-positive cancers, and clinic trials of pyrotinib in treatment of HER2-positive gastric cancer (GC) are underway. Exosomes are tiny vesicles secreted by cancer cells and take essential roles in the progression of carcinoma. Whether pyrotinib application has any effect on the cancer cell-released exosomes has not been studied. The aim of our work was to address if pyrotinib treatment impacts the effect of HER2-positive GC cell-derived exosomes on endothelial cell (EC) progression. Methods: Isolation of exosomes released by HER2-positive NCI-N87 and MKN45 lines after pyrotinib treatment was performed. Then, human umbilical vein endothelial cells (HUVECs) were incubated with different concentrations of exosomes to address their proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). Effect of pyrotinib-treated exosomes at concentration of 10 µg/mL was compared to that without pyrotinib treatment over 96-hr time course. Transwell assay and wound-healing assay were carried out by incubating with exosomes released by NCI-N87 and MKN45 cells with/without pyrotinib treatment over 24-hr time course. The aforementioned experiments were done under same conditions in order to evaluate the combined effect of apatinib and pyrotinib on HUVEC motility and invasive capacity. Results: We showed that HUVEC proliferation, motility and invasive capacity were further enhanced upon incubation with exosomes released by pyrotinib-treated GC cell lines, compared to those without pyrotinib treatment. Significantly, this effect was counteracted by the vascular endothelial growth factor receptor (VEGFR)-2 inhibitor apatinib which inhibits EC progression. Conclusion: Our study suggests that pyrotinib application on HER2-positive GC produces stronger exosomes that promote the proliferation and motility of vascular ECs, and combination of pyrotinib with apatinib provides potentially better therapy.

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Pyrotinib: First Global Approval

Cited by 123 publications

References 8 publications

Radiosensitization of HER2-positive esophageal cancer cells by pyrotinib

Radiosensitization of HER2-positive esophageal cancer cells by pyrotinib

Pyrotinib sensitizes 5‑fluorouracil‑resistant HER2-positive breast cancer cells to 5‑fluorouracil

<p>Pyrotinib treatment on HER2-positive gastric cancer cells promotes the released exosomes to enhance endothelial cell progression, which can be counteracted by apatinib</p>

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