Induction Chemotherapy for Head and Neck Cancer: Recent Data

Vokes, Everett E.

doi:10.1634/theoncologist.2010-s3-03

Cited by 46 publications

(35 citation statements)

References 15 publications

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“…Chemotherapy today remains the central therapeutic approach for the majority of cancer patients, as a treatment that places emphasis on the quality of life and the preservation of organ function (1,2). However, the application of chemotherapy is limited due to numerous obstacles, including adverse effects and multidrug resistance (MDR), which ultimately reduces treatment efficacy and are associated with disease progression (3,4).…”

Section: Introductionmentioning

confidence: 99%

Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells

et al. 2014

Molecular Medicine Reports

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Multidrug resistance (MDR) is one of the most important obstacles affecting the efficacy of chemotherapy treatments for numerous types of cancer. In the present study, we have demonstrated the possible function of Twist1 in the chemosensitivity of head and neck squamous cell carcinoma (HNSCC) and have identified that its mechanism maybe associated with MDR1/P-gp regulation. To investigate this, the hypopharyngeal cancer cell line, FaDu, and its MDR cell line induced by taxol, FaDu/T, were employed. Stable transfectants targeted to Twist1 overexpression and Twist1 silencing based on FaDu were also conducted. Morphological observation, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), western blotting and laser scanning confocal microscope detection were utilized to detect the associations between Twist1 and the chemosensitivity of FaDu cells. Our results demonstrated that Twist1 and MDR1/P-gp were upregulated in FaDu/T cells in a MDR dose-dependent manner. The anti-apoptotic capabilities of FaDu/T cells were enhanced during MDR progression, with apoptosis-related proteins (Bcl-2, Bax, activated caspase-3 and caspase-9) changing to resist apoptosis. Twist1 overexpression decreased the sensitivity of cells to taxol as revealed by a significant increase in MDR1/P-gp and IC50 (P<0.05). This overexpression also enhanced the resistance to apoptosis, with apoptotic proteins changing to resist cell death, and inhibited Ca2+ release induced by taxol (P<0.05). Detections in Twist1 silencing cells also confirmed this result. This study provided evidence that alterations of Twist1 expression modulates the chemosensitivity of FaDu cells to taxol. Therefore, Twist1 knockdown may be a promising treatment regimen for advanced hypopharyngeal carcinoma patients with MDR.

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Section: Introductionmentioning

confidence: 99%

Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells

et al. 2014

Molecular Medicine Reports

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“…[27],[28] While initial studies were mostly with the use of doublet-IC, recent studies have shown more favorable outcomes with the use of triplet regimens, by the addition of taxanes to the usual cisplatin and 5-fluorouracil. [29],[30] Response rates with IC are reportedly as high as <80%, with about half of the responding patients demonstrating complete responses. [27],[28]…”

Section: Discussionmentioning

confidence: 99%

Palliative radiotherapy in locally advanced head and neck cancer after failure of induction chemotherapy: Comparison of two fractionation schemes

Pandey¹,

Revannasiddaiah²,

Pant³

et al. 2013

Indian J Palliat Care

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Context:Among patients with locally advanced head and neck squamous cell cancers (LAHNSCC), the prognosis after nonresponse or progression despite induction chemotherapy (IC) is dismal, and further treatment is often palliative in intent. Given that nonresponse to chemotherapy could indicate subsequent radioresistance, we intended to assess the outcomes with two different fractionation schemes.Aims:To compare the outcomes of two fractionation schemes- ’standard’ (consisting 3GyX5 daily fractions for 2 consecutive weeks) versus ‘hybrid’ (6GyX3 fractions on alternate days during the 1st week, followed by 2GyX5 daily fractions in the 2nd week).Settings and Design:Prospective randomized controlled two-arm unblinded trial.Materials and Methods:Patients with locally advanced oropharyngeal, laryngeal, and hypopharyngeal cancers treated with a minimum of two cycles of taxane, platinum, and fluorouracil-based IC were eligible if residual disease volume amounted <30 cm3. Kaplan-Meier survival curves were compared by the log-rank test. Response rates were compared using the unpaired t-test. Quality of life (QOL) was measured via patient reported questionnaires.Results:Of the initially enrolled 51 patients, 45 patients (24 from standard arm, and 21 from the hybrid arm) were eligible for analysis. Despite being underpowered to attain statistical significance, there still seemed to be a trend towards improvement in progression-free (Hazard ratio (HR) for progression: 0.5966; 95% CI 0.3216-1.1066) and overall survival (HR for death: 0.6062; 95% CI 0.2676-1.3734) with the hybrid arm when compared to the standard arm. Benefits were also observed with regards to response rates and QOL. Rate of complications were similar in both arms.Conclusions:In comparison to the routinely used palliative fractionation scheme of 30 Gray (Gy) in 10 fractions (Fr), the use of hybrid fractionation which integrates hypofractionation in the 1st week, followed by conventional fractionation in the 2nd week, could possibly offer better response rates, QOL increments, and potential survival benefits among LAHNSCC patients even after failing to respond to IC.

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“…To determine whether the information of Twist1-Jagged1-KLF4 axis can provide a guide to specific treatment strategy for patients with Twist1-overexpressing cancers, Twist1-overexpressing OECM1 cells were used to test drug response. Two commonly used drugs for HNC treatment, cetuximab and cisplatin 30,31 , were individually tested with or without a g-secretase inhibitor N-[N- …”

Section: Oecm1-twist1mentioning

confidence: 99%

“…Antigen retrieval processes were then performed twice by pressure cooker at 1.2 atm for 15 min with target retrieval solution (#S1700, Dako, Denmark) and then blocked with 0.3% hydrogen peroxide for 30 min. Biotinylated probes (20 ml) for general screening (HPV 6,11,16,18,30,31,33,45, 51, 52; #Y1404, DAKO) were applied on separate specimen and were covered with coverslips. Denaturation of DNA was performed at 92°C for 5 min in an oven.…”

Section: Oecm1-mentioning

confidence: 99%

Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis

et al. 2014

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The mechanisms controlling tumour-induced angiogenesis are presently not clear. In principle, angiogenesis can be achieved through the activation of endothelial cells in existing vessels or by transdifferentiation of tumour cells into endothelial cells. However, whether tumour cells can go through a prior epithelial-mesenchymal transition and further differentiate into endothelial cells remains unknown. Here we show that overexpression of Twist1, a transcriptional regulator that induces and promotes cancer metastasis, leads to endothelial differentiation in head and neck cancer (HNC) cells. Induction of Jagged1 expression by Twist1 is essential for Twist1-induced endothelial differentiation. The Jagged1/ Notch signalling subsequently activates KLF4, inducing stem-like properties in HNC cells and conferring them with drug resistance. Our results indicate that the Twist1-Jagged1/KLF4 axis is essential both for transdifferentiation of tumour cells into endothelial cells and for chemoresistance acquisition.

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Induction Chemotherapy for Head and Neck Cancer: Recent Data

Cited by 46 publications

References 15 publications

Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells

Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells

Palliative radiotherapy in locally advanced head and neck cancer after failure of induction chemotherapy: Comparison of two fractionation schemes

Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis

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