EGFR Inhibitor Enhances Cisplatin Sensitivity of Oral Squamous Cell Carcinoma Cell Lines

Hiraishi, Yukihiro; Wada, Takuro; Nakatani, Ken; Tojyo, Itaru; Mutoh, T.; Kiga, Norifumi; Negoro, Kohei; Fujita, Shigeyuki

doi:10.1007/s12253-008-9020-5

Cited by 43 publications

(48 citation statements)

References 26 publications

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“…These signal transduction pathways activated by pEGFR are important in cell differentiation, proliferation, migration, adhesion and apoptosis (15). It has been reported that the chemoresistance of several types of tumors including bladder cancer are associated with EGFR and pEGFR overexpression (16,17). These findings indicated that LRIG1 may enhance the sensitivity of cancer cells to chemotherapeutic agents.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

et al. 2015

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Abstract. Cisplatin (cis-diaminodichloroplatinum, CDDP) is one of the most effective chemotherapeutic agents that has been widely used in the treatment of many malignancies, including muscle invasive bladder cancer. However, development of CDDP resistance in cancer cells is a major obstacle to the effective treatment of bladder cancer. Therefore, the development of chemosensitizers to overcome the acquired resistance to chemotherapeutic agents is crucial. Previous studies have confirmed that the epidermal growth factor receptor (EGFR) and its signaling pathways are important in the chemoresistance of cancer cells against CDDP-induced cell apoptosis. In a preliminary study we showed that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is the natural ligand of EGFR, and that the extracellular leucine-rich repeat (LRR) domain and immunoglobulin-like domains of LRIG1 were able to bind to the extracellular domain of EGFR, resulting in the downregulation of EGFR expression. Based on these findings, we hypothesized that LRIG1 may enhance the chemosensitivity of bladder cancer cells to CDDP. In the present study, LRIG1 was overexpressed by the adenovirus vector to determine the effect of LRIG1 on chemosensitivity in the T24 bladder cancer cell line and explored the possible mechanisms. The results showed that CDDP inhibited the growth of the T24 cell line and induced activation of EGFR. Overexpression of LRIG1 increased the inhibitory effect of CDDP on the T24 cell line, which may be associated with inactivation of the EGFR signaling pathway, followed by the decrease of Bcl-2 expression and a concomitantly induced expression of Bax. Based on these results, we concluded that the upregulation of LRIG1 expression inhibited the EGFR signaling pathway, activated the mitochondrial pathway of apoptosis and eventually increased the sensitivity of bladder cancer cells to CDDP. IntroductionBladder cancer is the fourth most common malignant disease worldwide, accounting for ~6% of all cancer cases (1). Bladder cancers (75%) are non-muscle-invasive and can be treated by transurethral resection of the bladder tumor combined with intravesical chemotherapeutic agents instillation. However, the prognosis of patients with muscle invasive bladder cancer (25%) remains poor despite the many advances in treatments made over the past few decades. To improve survival rate and extend life span, patients with muscle invasive bladder cancer require chemotherapy after surgery (2). Cisplatin (CDDP)-based chemotherapy is widely used for treatment of muscle invasive bladder cancer (3). However, cancer cell resistance to CDDP is a major obstacle to the effective treatment of bladder cancer, and the underlying mechanism of the resistance is unclear.The molecular mechanisms of CDDP include binding of the drug to DNA and non-DNA targets to form a variety of monoadducts and cross links, which contribute to the cytotoxicity of CDDP by blocking DNA replication and stimulating signals for apoptosis (4). Despite the excellent anticancer effect...

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Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

et al. 2015

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“…A panel of four cisplatin-resistant neuroblastoma cell lines have also been shown to have increased EGFR and pEGFR protein expression and be more sensitive to treatment with novel EGFR-targeted agents than their cisplatin-sensitive counterparts (Michaelis et al, 2008). Similar results were seen in two cisplatin-resistant oral carcinoma cell lines, increased EGFR and pEGFR and sensitivity to the novel EGFR inhibitor AG1478 (Hiraishi et al, 2008). Therefore, treatment with platinum and the development of platinum resistance may cause EGFR dysfunction by altering the protein expression and activity of components of the EGFR pathway in a subpopulation of relapsed cancer patients.…”

Section: Introductionmentioning

confidence: 61%

Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: A systematic review

Murphy

Stordal

2011

Drug Resistance Updates

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Copyright and moral rights to this thesis/research project are retained by the author and/or other copyright owners. The work is supplied on the understanding that any use for commercial gain is strictly forbidden. A copy may be downloaded for personal, non-commercial, research or study without prior permission and without charge. Any use of the thesis/research project for private study or research must be properly acknowledged with reference to the work's full bibliographic details.This thesis/research project may not be reproduced in any format or medium, or extensive quotations taken from it, or its content changed in any way, without first obtaining permission in writing from the copyright holder(s).If you believe that any material held in the repository infringes copyright law, please contact the Repository Team at Middlesex University via the following email address:The item will be removed from the repository while any claim is being investigated. Methods: A systematic review was conducted to investigate whether two EGFR-TKIs, erlotinib and gefitinib, have efficacy in the platinum-resistance setting. Preclinical studies of platinum-resistant cancer cell lines, which had been subsequently treated with EGFRTKIs, were sought to establish proof-of-concept. Clinical trials reporting administration of EGFR-TKIs to ovarian cancer and NSCLC patients relapsed after therapy with platinum drugs were investigated to determine sensitivity of these cohorts to EGFR-TKI treatment. The role of EGFR mutation, copy number and protein expression on response to EGFR-TKIs after failure of platinum chemotherapy were also investigated.Results: Preclinical models of platinum-resistant cancer were found which display a spectrum of cross-resistance profiles to EGFR-TKIs. Sensitivity to EGFR-TKIs is dependent on the activation of the EGFR pathway or EGFR interacting proteins such as HER-2. EGFR-TKIs show favourable response rates in platinum-pretreated NSCLC, 11.14% and 15.25% for 150 mg/day erlotinib and 250 mg/day gefitinib, respectively. These response rates significantly improve in patients of Asian descent (28.3% and 29.17%, respectively) and patients with EGFR activation mutations (41.6% and 63.89%, respectively) or increased copy number (33.3% and 45.45%, respectively). Gefitinib significantly outperformed erlotinib and should therefore be the EGFR-TKI of choice in platinum-pretreated relapsed NSCLC. In contrast, response rates are very poor to both erlotinib and gefitinib in platinum pretreated ovarian cancer, 0-5.9% and they should not be used in this cohort of patients.Preclinical models demonstrate that, while cross resistance can occur between platinums and EGFR-TKIs, there is not a generalised cross-resistance phenotype. Erlotinib and gefitinib are suitable for the treatment of platinum-pretreated NSCLC, particularly in patients with EGFR mutations or increases in copy number. Unfortunately, the high rates of EGFR protein overexpression in ovarian cancer are not translating to a clinically useful therapeutic target for ...

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“…[24] Lapatinib inhibits the tyrosine kinase activity associated with EGFR and human EGFR 2 (HER 2). [25] A pilot phase II study was conducted by Pfister et al to generate pilot data for a novel paradigm for combined-modality therapy through the integration of a biologically active, targeted agent with an established concurrent chemoradiotherapy program.…”

Section: Combination Therapy With Egfr Inhibitorsmentioning

confidence: 99%

Specific role of targeted molecular therapy in treatment of oral squamous cell carcinoma

Gupta¹,

Sivasankari²

2017

Oncobiology and Targets

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Oral cancer is a potentially fatal disease that constitutes an important portion of tumors that occur in the head and neck region. Oral cancer can affect overall and mental health, appearance, employment, social life, and family living. The disease can cause serious changes in the functioning of the upper aero digestive tract that affects the quality of life in patients. The use of conventional treatment modalities (surgery, radiation, and/or chemotherapy) depends on tumor respectability and location as well as whether an organ preservation approach is feasible. However, their role in oral cancer treatment is nonselective and can cause damage to normal tissue. In particular, chemo radiotherapy is associated with systemic toxicities that often reduce patient compliance and prevent timely completion of therapy. The development of targeted therapies to target select pathways involved in carcinogenesis, potentially decrease systemic toxicities and morbidities associated with cancer burden and hence improve the prognosis in cancer patients. In the present article, the role of various targeted molecules in the treatment of oral cancer is discussed.

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EGFR Inhibitor Enhances Cisplatin Sensitivity of Oral Squamous Cell Carcinoma Cell Lines

Cited by 43 publications

References 26 publications

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: A systematic review

Specific role of targeted molecular therapy in treatment of oral squamous cell carcinoma

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