Phase II study of erlotinib and docetaxel with concurrent intensity‐modulated radiotherapy in locally advanced head and neck squamous cell carcinoma

Yao, Min; Woods, Charles R.; Fu, Pingfu; Gibson, Michael K.; Rezaee, Rod; Zender, Chad; Wasman, Jay; Sharma, Neelesh; Machtay, Mitchell; Savvides, P.

doi:10.1002/hed.24313

Cited by 13 publications

(5 citation statements)

References 32 publications

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“…Many studies have reported that CSCs contributed to chemoresistance 5 , 30 . Erlotinib is a small-molecule tyrosine kinase inhibitor that inhibits the kinase domain of the EGFR 31 and has been tested in the clinic as treatments for recurrent and/or metastatic HNSCC 32 – 34 . We determined to test whether PTK7 inhibition reduced tumor progression and increased erlotinib sensitivity in vivo.…”

Section: Resultsmentioning

confidence: 99%

RETRACTED ARTICLE: Periostin secreted by cancer-associated fibroblasts promotes cancer stemness in head and neck cancer by activating protein tyrosine kinase 7

et al. 2018

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Protein tyrosine kinase 7 (PTK7) and cancer-associated fibroblasts (CAFs) play important roles in cancer stemness, respectively. However, little is known about interaction between CAFs and PTK7 in cancers. In this study, we showed that PTK7 was significantly correlated with the Wnt/β-Catenin pathway and aggressive clinicopathologic features in human head and neck squamous cell carcinoma (HNSCC). Meanwhile, animal experiments showed that PTK7 enhanced chemoresistance and lung metastasis of HNSCC in vivo. In addition, co-immunoprecipitation (co-IP) assay demonstrated that POSTN secreted by CAFs was a potential upstream ligand of PTK7 which might act as a receptor. Further analysis revealed that POSTN promoted the cancer stem cell (CSC)-like phenotype via PTK7–Wnt/β-Catenin signaling, including the proliferation and invasion of HNSCC cells in vitro, as well as tumor initiation and progression in vivo. Collectively, our study proved that CAF-derived POSTN might promote cancer stemness via interacting with PTK7 in HNSCC, suggesting that the combination of POSTN and PTK7 might be a potential prognostic and diagnostic indicator and a promising therapeutic target.

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Section: Resultsmentioning

confidence: 99%

RETRACTED ARTICLE: Periostin secreted by cancer-associated fibroblasts promotes cancer stemness in head and neck cancer by activating protein tyrosine kinase 7

et al. 2018

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“…Overexpression of epidermal growth factor receptor (EGFR) and its ligands have been observed in nearly 80–90% of cases of head and neck squamous cell carcinoma (HNSCC) and correlates with poor prognosis and resistance to radiation (Bauman et al 2017; Cassell and Grandis 2010). Erlotinib is an oral tyrosine kinase inhibitor (TKI) of EGFR, approved in the United States as treatment for advanced pancreatic and non–small‐cell lung cancer (Yao et al 2016). Preclinical models suggest a significant radiotherapy‐sensitizing effect and a potential synergism with cisplatin (Martins et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Identification of extracellular vesicles-transported miRNAs in Erlotinib-resistant head and neck squamous cell carcinoma

Zheng

Zhou

et al. 2020

J. Cell Commun. Signal.

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Erlotinib is an oral tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) pathway. Although our previous study has proved the efficacy of Erlotinib in head and neck squamous cell carcinoma (HNSCC), it has also demonstrated poor clinical response rates and disappointing results in clinical trials for HNSCC to date. In this study, we discovered elevated cell proliferation and invasion ability in erlotinib‐resistant HNSCC cells. The contributions of miRNAs within extracellular vesicles (EVs) during the formation of chemoresistance were investigated in this study. Among up‐regulated miRNAs in EVs derived from resistant cells, miR‐7704, miR‐21‐5p and miR‐3960 showed the most pro‐tumorigenic alterations after transfection. Conversely, let‐7i‐5p, miR‐619‐5p and miR‐30e‐3p demonstrated tumor suppressive effects. By performing qRT‐PCR and Western blot analysis, we found Vimentin played a pivotal role in modulating erlotinib resistance. Additionally, immune system was highlighted in the GO and KEGG analyses. Transfection of miR‐7704, miR‐21‐5p significantly elevated CTLA‐4 and LAG3 mRNA levels. Meanwhile, miR‐3960 increased the relative mRNA expression of TIM3 in HNSCC cells. Transfection of let‐7i‐5p, miR‐619‐5p and miR‐30e‐3p decreased these checkpoint factors. To conclude, the present study described the roles of EVs‐transmitted miRNAs on erlotinib resistance. Targeting the disregulated immune system could be the effective method to overcome erlotinib‐resistance in HNSCC cells.

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“…In the present study, erlotinib combined with DDP and irradiation showed the most significant reduction in cell viability, invasion and migration ability and the highest increase in apoptosis, when compared to other treatment strategies. These results indicated that erlotinib enhanced the sensitivity of cells to irradiation or/and DDP (24)(25)(26).…”

Section: Discussionmentioning

confidence: 79%

Erlotinib enhanced chemoradiotherapy sensitivity via inhibiting DNA damage repair in nasopharyngeal carcinoma CNE2 cells

et al. 2020

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Background: Nasopharyngeal carcinoma (NPC), arising from nasopharynx epithelium, is a rare type of malignant carcinoma that has a specific geographical distribution and a high risk of distant metastases. For most of the diagnosed NPC patients, the total survival rate decreased significantly due to the high local recurrence rate and metastasis rate. Concurrent chemoradiotherapy (CCRT), as routine therapy strategy of NPC, usually accompanies with high-dosage cytotoxic agents and serious toxic side reaction. Therefore, there is an urgent need for update the existing therapy strategies. In this study, we sought to investigate the effects of a combined therapy strategy, erlotinib combined with cisplatin and radiotherapy, on biological characteristics of NPC CNE2 cells and the potential reasons.Methods: CNE2 cells in logarithmic phase seeding in 96-well plates received concentration gradients of erlotinib (at 0, 10, 20, 40, 80, 160, 320 mmol/L) or cisplatin (at 0, 0.25, 0.5, 1, 2, 4, 8 mg/L), in order to obtain the optimal working concentration of erlotinib and cisplatin via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Then, cells were divided into control group and four treatment groups (Group I-IV). All treatment groups received irradiation of 4 Gy, moreover, Group II-IV respectively received erlotinib, cisplatin and erlotinib plus cisplatin at optimal working concentration. After 24 and 48 h of irradiation, growth inhibition rate was determined; invasion ability and migration ability was respectively detected by Boyden's chamber assay and cell scratch test; flow cytometry was performed for determining apoptosis rate and cell cycle distribution; the expression levels of epidermal growth factor receptor (EGFR) signal pathway proteins were semi-quantitatively analyzed by Western-blot.Results: Compared with Group I, all the other treatment groups showed better inhibition effect on cell viability, invasion and migration ability and higher apoptosis rate, while Group IV showed the strongest growth inhibition effect and highest apoptosis rate. In addition, EGFR signal pathway proteins of Group IV showed the lowest expression level. Conclusions:In combined therapy with radiotherapy/chemotherapy, erlotinib could enhance radiotherapy/chemotherapy sensitivity, probably because it could suppress DNA damage repair after radiotherapy/chemotherapy, thus weakening radiotherapy/chemotherapy resistance of tumor cells.

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Phase II study of erlotinib and docetaxel with concurrent intensity‐modulated radiotherapy in locally advanced head and neck squamous cell carcinoma

Cited by 13 publications

References 32 publications

RETRACTED ARTICLE: Periostin secreted by cancer-associated fibroblasts promotes cancer stemness in head and neck cancer by activating protein tyrosine kinase 7

RETRACTED ARTICLE: Periostin secreted by cancer-associated fibroblasts promotes cancer stemness in head and neck cancer by activating protein tyrosine kinase 7

Identification of extracellular vesicles-transported miRNAs in Erlotinib-resistant head and neck squamous cell carcinoma

Erlotinib enhanced chemoradiotherapy sensitivity via inhibiting DNA damage repair in nasopharyngeal carcinoma CNE2 cells

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