c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation

Baschnagel, Andrew M.; Williams, Letitia; Hanna, Alaa; Chen, Peter Y.; Krauss, Daniel; Pruetz, Barbara L.; Åkervall, Jan; Wilson, George D.

doi:10.1016/j.ijrobp.2013.11.013

Cited by 44 publications

(31 citation statements)

References 21 publications

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“…4 and Table S4). Controversial findings exist regarding the prognostic significance of c-Met in HNSCC (11, 35, 36). These discrepancies are likely due to differences in the tumor sites investigated, analytical methods used (whether HPV status is stratified, e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Upon binding to its sole ligand, hepatocyte growth factor (HGF), c-Met activates multiple downstream pathways, including PI3K/AKT and RAS/MAPK pathways, to promote proliferation, migration, invasion and metastasis (10). Furthermore, c-Met expression has been associated with worse outcomes in patients with locally advanced HNSCC (11) and targeting c-Met using monoclonal antibodies and specific kinase inhibitors has been proposed in clinical trials (12–14). c-Met expression and its correlation with clinical-pathological features in HNSCC have been summarized in a review article by Nisa et al (14).…”

Section: Introductionmentioning

confidence: 99%

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Human papillomavirus oncoprotein E6 upregulates c-Met through p53 downregulation

Qian

Wang

Magliocca

et al. 2016

European Journal of Cancer

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Purpose Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) carries a distinct clinical behavior. c-Met oncogene is an important driver for tumor progression and its relationship with HPV in OPSCC was explored in the current study. Experimental Design Knockdown of HPV oncogene E6 or p53 alone and in combination was performed to examine their effects on c-Met expression by western blot and qRT-PCR. The effects of c-Met inhibition on cell proliferation, migration, and colony formation were examined in HPV-positive head and neck squamous cell carcinoma (HNSCC) cells. Retrospectively collected OPSCC patient specimens (N = 78) were stained for c-Met by immunohistochemistry and the staining levels were correlated with HPV status and patient outcomes. Results E6 knockdown decreased c-Met protein and mRNA expression in HPV-positive HNSCC cells, which was partially abolished by the elimination of p53. Reducing c-Met decreased cell proliferation, migration, and colony formation in HPV-positive HNSCC cells. In OPSCC patient samples, high c-Met expression was associated with HPV positive status (OR = 4.11, 95%CI: 1.16–14.55, P = 0.028) and tumor stage (OR = 0.27, 95%CI: 0.08–0.93, P = 0.039) by multivariable analysis. In T3/T4 stage patients, high c-Met expression was associated with HPV positivity and low p53 levels, supporting an axis of E6-p53-c-Met regulation. Furthermore, high c-Met expression was marginally associated with poor disease-free survival in HPV-positive patients. Conclusions Our results suggest that c-Met may serve as a novel target for treating HPV-associated OPSCC. The data also demonstrates that HPV E6 upregulates c-Met expression partially through p53 downregulation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human papillomavirus oncoprotein E6 upregulates c-Met through p53 downregulation

Qian

Wang

Magliocca

et al. 2016

European Journal of Cancer

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“…On the other hand, radiation can also promote immune responses through the induction of neoantigens and the stimulation of factors such as interferon-γ (IFNγ) that can enhance T-cell infiltration (26). This dual ability to control local tumor progression and to influence metastatic spread and immune response constitute a compelling argument for including radiation in combination with the current arsenal of immune checkpoint inhibitors now entering the clinic.…”

Section: Radiation In the Treatment Of Solid Tumorsmentioning

confidence: 99%

Combining Radiation and Immunotherapy: A New Systemic Therapy for Solid Tumors?

Tang

Wang

Soh

et al. 2014

Cancer Immunology Research

287

205

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With the recent success of checkpoint inhibitors and other immune-modulating agents, there has been renewed interest in the combination of such agents with radiation. The biological premise behind such a strategy is that the tumor-antigen release achieved by localized radiation will promote specific tumor-targeting by the adaptive immune system, which can be augmented further by systemic immune-stimulating agents. In this manner, clinicians hope to induce a phenomenon known as the abscopal effect, whereby localized radiation results in immune-mediated tumor regression in disease sites well outside of the radiation field. In this Crossroads in Cancer Immunology article, we will present a comprehensive overview of the early clinical and pre-clinical evidence behind this approach.

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“…Studies comparing c-Met expression with clincopathological parameters consistently report positive and overexpressed c-Met protein in HNSCC tumor samples [73,76,77,78]. However, the value of tumoral c-Met expression as an independent prognostic indicator in HNSCC remains controversial due to inconsistent reports regarding which clinical parameters significantly correlate with c-Met expression (Table 1).…”

Section: Relation Of the Hgf/c-met Pathway To Hnscc Outcomementioning

confidence: 99%

Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment

Rothenberger

Stabile

2017

Cancers

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Aberrant signaling of the hepatocyte growth factor (HGF)/c-Met pathway has been identified as a promoter of tumorigenesis in several tumor types including head and neck squamous cell carcinoma (HNSCC). Despite a relatively low c-Met mutation frequency, overexpression of HGF and its receptor c-Met has been observed in more than 80% of HNSCC tumors, with preclinical and clinical studies linking overexpression with cellular proliferation, invasion, migration, and poor prognosis. c-Met is activated by HGF through a paracrine mechanism to promote cellular morphogenesis enabling cells to acquire mesenchymal phenotypes in part through the epithelial-mesenchymal transition, contributing to metastasis. The HGF/c-Met pathway may also act as a resistance mechanism against epidermal growth factor receptor (EGFR) inhibition in advanced HNSCC. Furthermore, with the identification of a biologically distinct subset of HNSCC tumors acquired from human papillomavirus (HPV) infection that generally portends a good prognosis, high expression of HGF or c-Met in HPV-negative tumors has been associated with worse prognosis. Dysregulated HGF/c-Met signaling results in an aggressive HNSCC phenotype which has led to clinical investigations for targeted inhibition of this pathway. In this review, HGF/c-Met signaling, pathway alterations, associations with clinical outcomes, and preclinical and clinical therapeutic strategies for targeting HGF/c-Met signaling in HNSCC are discussed.

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c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation

Cited by 44 publications

References 21 publications

Human papillomavirus oncoprotein E6 upregulates c-Met through p53 downregulation

Human papillomavirus oncoprotein E6 upregulates c-Met through p53 downregulation

Combining Radiation and Immunotherapy: A New Systemic Therapy for Solid Tumors?

Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment

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