Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells

Huang, Feifei; Liang, Xujun; Min, Xiaoli; Zhang, Ye; Wang, Guoqiang; Peng, Zhengrong; Peng, Fang; Li, Maoyu; Lin, Chen; Chen, Yongheng

doi:10.7150/jca.29327

Cited by 10 publications

(12 citation statements)

References 41 publications

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“…Another group of EGFR inhibitors, tyrosine kinase inhibitors including gefitinib and erlotinib, failed to show promising results in patients with recurrent/metastatic NPC [41]. However, a new generation of EGFRi, AFA, which is an irreversible EGFR/HER2 inhibitor, was found to inhibit cell growth, augment the anticancer effect of gemcitabine [42], and enhance radiosensitivity in NPC [43]. In the current study, we showed that either ERB or AFA could inhibit NPC PDX tumor growth.…”

Section: Egfr Is a Target In Npc Managementmentioning

confidence: 53%

Combination of Epithelial Growth Factor Receptor Blockers and CDK4/6 Inhibitor for Nasopharyngeal Carcinoma Treatment

Huang

Lui

et al. 2021

Cancers

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Background: Nasopharyngeal carcinoma (NPC) involves host genetics, environmental and viral factors. In clinical observations, patients of young and old ages were found to have higher recurrence and metastatic rates. Methods: Cytokine array was employed to screen druggable target(s). The candidate target(s) were confirmed through patient-derived xenografts (PDXs) and a new EBV-positive cell line, NPC-B13. Results: Overexpression of epithelial growth factor (EGF) and EGF receptor (EGFR) was detected in young patients than in older patients. The growth of NPC PDX tumors and cell lines was inhibited by EGFR inhibitors (EGFRi) cetuximab and afatinib when used separately or in combination with the cell cycle blocker palbociclib. Western blot analysis of these drug-treated PDXs demonstrated that the blockade of the EGF signaling pathway was associated with a decrease in the p-EGFR level and reduction in PDX tumor size. RNA sequencing results of PDX tumors elucidated that cell cycle-related pathways were suppressed in response to drug treatments. High EGFR expression (IHC score ≥ grade 3) was correlated with poor survival in metastatic patients (p = 0.008). Conclusions: Our results provide encouraging preliminary data related to the combination treatment of EGFRi and palbociclib in patients with NPC.

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Section: Egfr Is a Target In Npc Managementmentioning

confidence: 53%

Combination of Epithelial Growth Factor Receptor Blockers and CDK4/6 Inhibitor for Nasopharyngeal Carcinoma Treatment

Huang

Lui

et al. 2021

Cancers

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Section: The Role Of Egfr Targeting In Nasopharyngeal Carcinomamentioning

confidence: 99%

“…Afatinib inhibits EGFR and ErbB-2 tyrosine kinase activity and suppresses NPC cell proliferation by arresting the cell cycle [ 108 ]. The combination of Afatinib and Gemcitabine (GEM) have shown significant anti-tumor efficacy in NPC xenograft models [ 108 , 109 ]. In addition, Erlotinib and Afatinib could enhance the sensitivity of tumors to chemoradiotherapy by inhibiting DNA damage repair [ 105 , 108 ].…”

Section: The Role Of Egfr Targeting In Nasopharyngeal Carcinomamentioning

confidence: 99%

“…The combination of Afatinib and Gemcitabine (GEM) have shown significant anti-tumor efficacy in NPC xenograft models [ 108 , 109 ]. In addition, Erlotinib and Afatinib could enhance the sensitivity of tumors to chemoradiotherapy by inhibiting DNA damage repair [ 105 , 108 ]. However, no clinical trials have shown that TKIs can significantly improve the prognosis of NPC patients [ 107 , 118 ].…”

Section: The Role Of Egfr Targeting In Nasopharyngeal Carcinomamentioning

confidence: 99%

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Nasopharyngeal Carcinoma: The Role of the EGFR in Epstein–Barr Virus Infection

et al. 2021

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Epstein–Barr virus (EBV), a type 4 γ herpes virus, is recognized as a causative agent in nasopharyngeal carcinoma (NPC). Incidence of EBV-positive NPC have grown in recent decades along with worse outcomes compared with their EBV-negative counterparts. Latent membrane protein 1 (LMP1), encoded by EBV, induces NPC progression. The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases (RTK), is a driver of tumorigenesis, including for NPC. Little data exist on the relationship between EGFR and EBV-induced NPC. In our initial review, we found that LMP1 promoted the expression of EGFR in NPC in two main ways: the NF-κB pathway and STAT3 activation. On the other hand, EGFR also enhances EBV infection in NPC cells. Moreover, activation of EGFR signalling affects NPC cell proliferation, cell cycle progression, angiogenesis, invasion, and metastasis. Since EGFR promotes tumorigenesis and progression by downstream signalling pathways, causing poor outcomes in NPC patients, EGFR-targeted drugs could be considered a newly developed anti-tumor drug. Here, we summarize the major studies on EBV, EGFR, and LMP1-regulatory EGFR expression and nucleus location in NPC and discuss the clinical efficacy of EGFR-targeted agents in locally advanced NPC (LA NPC) and recurrent or metastatic NPC (R/M NPC) patients.

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“…It has been reported that AFT decreases the levels of phospho-EGFR and phospho-HER2 and remarkably inhibits cancer cell proliferation and survival. 27,28 Downregulation of EGFR or HER2 directly inhibits PI3K/Akt/mTOR signaling, triggering apoptosis. 29,30 In NPC, CDDP treatment (alone)…”

Section: Apoptotic Effects Of the Drug Combination On Hone1 Cellsmentioning

confidence: 99%

Lipid–Polymer Hybrid Nanoparticle-Based Combination Treatment with Cisplatin and EGFR/HER2 Receptor-Targeting Afatinib to Enhance the Treatment of Nasopharyngeal Carcinoma

Fu¹,

Li²,

Huang³

2021

OTT

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Purpose: Nasopharyngeal carcinoma (NPC) is one of the most prevalent carcinomas among the Cantonese population of South China and Southeast Asia (responsible for 8% of all cancers in China alone). Although concurrent platinum-based chemotherapy and radiotherapy have been successful, metastatic NPC remains difficult to treat, and the failure rate is high. Methods: Thus, we developed stable lipid-polymer hybrid nanoparticles (NPs) containing cisplatin (CDDP) and afatinib (AFT); these drugs act synergistically to counter NPC. The formulated nanoparticles were subjected to detailed in vitro and in vivo analysis. Results: We found that CDDP and AFT exhibited synergistic anticancer efficacy at a specific molar ratio. NPs were more effective than a free drug cocktail (a combination) in reducing cell viability, enhancing apoptosis, inhibiting cell migration, and blocking cell cycling. Cell viability after CDDP monotherapy was as high as 85.1%, but CDDP+AFT (1/1 w/w) significantly reduced viability to 39.5%. At 1 µg/mL, AFT/CDDP-loaded lipid-polymer hybrid NPs (ACD-LP) were significantly more cytotoxic than the CDDP+AFT cocktail, indicating the superiority of the NP system. Conclusion:The NPs significantly delayed tumor growth compared with either CDDP or AFT monotherapy and were not obviously toxic. Overall, the results suggest that AFT/ CDDP-loaded lipid-polymer hybrid NPs exhibit great potential as a treatment for NPC.

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Simultaneous Inhibition of EGFR and HER2 via Afatinib Augments the Radiosensitivity of Nasopharyngeal Carcinoma Cells

Cited by 10 publications

References 41 publications

Combination of Epithelial Growth Factor Receptor Blockers and CDK4/6 Inhibitor for Nasopharyngeal Carcinoma Treatment

Combination of Epithelial Growth Factor Receptor Blockers and CDK4/6 Inhibitor for Nasopharyngeal Carcinoma Treatment

Nasopharyngeal Carcinoma: The Role of the EGFR in Epstein–Barr Virus Infection

Lipid–Polymer Hybrid Nanoparticle-Based Combination Treatment with Cisplatin and EGFR/HER2 Receptor-Targeting Afatinib to Enhance the Treatment of Nasopharyngeal Carcinoma

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