Targeted therapies in head and neck cancer

Specenier, Pol; Vermorken, Jan B.

doi:10.1007/s11523-007-0048-3

Cited by 24 publications

(17 citation statements)

References 142 publications

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“…The results were consistent with our previous results which depicted upregulation of MMP-2 and MMP-9 in oral cancer (Shrestha et al, 2014). Earlier studies have observed that MMP-9 expression was associated with tumor metastasis of oral squamous cell carcinoma (OSCC) Specenier et al, 2015). Bhairavi N. Vajaria, Kinjal R. Patel, Rasheedunnisa Begum, Franky D. Shah, Jayendra B. Patel, Geeta M. Joshi, and Prabhudas S. Patel / American Journal of Oral medicine (2017) Vol.…”

Section: Discussionsupporting

confidence: 93%

Correlation between Loss of E-cadherin, Matrix-metalloproteinases and c-Jun expression in Oral Carcinogenesis

Vajaria¹,

Patel²,

Begum³

et al. 2017

AJOM

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Background: Earlier invitro studies have observed that loss of E-cadherin is responsible for progression and metastasis of cancer by upregulation of c-Jun protein. There being lack of simultaneous evaluation of matrix metalloproteinase (MMP) -2 and -9, E-cadherin and c-Jun mRNA and protein.Objective: This study aimed to correlate the above-mentioned parameters to evaluate the pathway of oral carcinogenesis. Methods:The study included 100 controls, 50 patients with oral precancerous conditions (OPC) and 100 oral cancer patients. MMPs were evaluated by gelatin zymography, ECAD and CJUN mRNA and protein expression by semi quantitative RT-PCR and western blot respectively. Results:The levels of active and total MMP-2 and MMP-9 were significantly higher in patients with OPC and oral cancer patients as compared to controls. A significant increase in truncated E-cadherin and c-Jun protein was observed in malignant tissues as compared to adjacent normal tissues while CJUN mRNA levels were comparable. Higher values of c-Jun protein and MMPs, and lower values of ECAD mRNA were associated with reduced overall survival. A positive correlation was observed between truncated E-cadherin, MMPs and c-Jun protein. Conclusions:MMPs modulate cell-cell adhesion by increasing truncation of E-cadherin resulting in loss of Ecadherin which is responsible for upregulation of c-Jun protein in oral cancer.

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Section: Discussionsupporting

confidence: 93%

Correlation between Loss of E-cadherin, Matrix-metalloproteinases and c-Jun expression in Oral Carcinogenesis

Vajaria¹,

Patel²,

Begum³

et al. 2017

AJOM

View full text Add to dashboard Cite

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“…Zalutumumab or panitumumab are just two clinically successful examples of monoclonal antibodies inhibiting EGFR [41]; they may provide promising new perspectives [24].…”

Section: Second-line Chemotherapy In Head and Neck Cancermentioning

confidence: 99%

Second-line chemotherapy in head and neck cancer: what should we expect?

Büntzel¹,

Micke²

2009

Expert Review of Anticancer Therapy

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“…Current trials show that induction chemotherapy using the triple combination followed by radiochemotherapy is more effective than radiochemotherapy based on cisplatin alone. However, this regime also shows high toxicity, particularly hematological toxicity.Targeted therapies are now providing new hope [3]. We are beginning to understand the role of growth factors, their receptors and signaling pathways in the cancer genesis and progression.…”

mentioning

confidence: 99%

“…Targeted therapies are now providing new hope [3]. We are beginning to understand the role of growth factors, their receptors and signaling pathways in the cancer genesis and progression.…”

mentioning

confidence: 99%

New therapies in squamous cell carcinoma of the head and neck: is the future in combined therapies?

Schneider

2008

Targ Oncol

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Every year there are more than 500,000 new cases of head and neck cancer throughout the world, primarily squamous cell carcinoma. For stage I and II cancers, surgery and radiotherapy allow progression-free survival for 5 years in 60% to 90% of the cases, depending on its localization. However, more than 50% of patients have advanced lesions at the time of diagnosis and will have local recurrence and distant metastasis.At the end of the 1970s, cisplatin was the first product to demonstrate a significant effect on this type of cancer, with a 30% objective response rate. Al Sarraf et al.'s [1] protocol associating cisplatin and 5-fluorouracile (5Fu) in a neoadjuvant setting gave a clinical objective response rate of 90%, with a 25% complete response rate. Yet randomized trials demonstrated that, with a few exceptions, although this induction chemotherapy lowers the rate of distant metastasis, it does not significantly increase survival and its indication must take into consideration organ preservation, notably for the larynx.A number of randomized trials have shown that radiochemotherapy either concurrently or alternately associating a platinum compound or its combination with 5Fu with radiotherapy was more effective than radiotherapy alone and significantly increased survival [2]. Recently, taxanes were shown to be active and the association of docetaxel and cisplatin-5Fu proved to be more effective than the traditional combination of cisplatin-5Fu. Current trials show that induction chemotherapy using the triple combination followed by radiochemotherapy is more effective than radiochemotherapy based on cisplatin alone. However, this regime also shows high toxicity, particularly hematological toxicity.Targeted therapies are now providing new hope [3]. We are beginning to understand the role of growth factors, their receptors and signaling pathways in the cancer genesis and progression. Epidermal growth factor receptor (EGFR), a member of the HER1 family, is overexpressed in more than 90% of squamous cell carcinoma of the head and neck (SCCHN). Overexpression of EGFR or of its main ligands, EGF and transforming growth factor alpha (TGFα), indicate an unfavorable prognosis. As a result, EGFR is considered to be a potential target for these new therapeutic approaches. There are several monoclonal antibodies and tyrosine kinase inhibitors (TKIs) that target EGFR and its mutated forms.Cetuximab (IMC 225) was the first monoclonal antibody used. It is a human/murine lgG1 chimeric antibody that binds more to the EGFR extracellular domain than to its EGF and TGFα ligands. It has antitumor activity on its own and creates synergies with chemotherapy and radiotherapy. The most frequent side effects are fever, asthenia, nausea, transaminases increase and, particularly, skin toxicities in the form of rashes. A recent study on numerous patients with stage III and IV SCCHN clearly indicated that the association of radiotherapy and cetuximab very significantly increased local control and survival when compared with radiotherapy alo...

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Targeted therapies in head and neck cancer

Abstract: Over the past decade, the important role of different growth factors and their receptors and signal transduction pathways in the genesis and progression of tumors has been well recognized and their mechanism of action and interactions is gradually being unraveled.

Cited by 24 publications

References 142 publications

Correlation between Loss of E-cadherin, Matrix-metalloproteinases and c-Jun expression in Oral Carcinogenesis

Correlation between Loss of E-cadherin, Matrix-metalloproteinases and c-Jun expression in Oral Carcinogenesis

Second-line chemotherapy in head and neck cancer: what should we expect?

New therapies in squamous cell carcinoma of the head and neck: is the future in combined therapies?

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