EGFR-TK inhibition before radiotherapy reduces tumour volume but does not improve local control: Differential response of cancer stem cells and nontumourigenic cells?

Krause, Mechthild; Prager, J; Zhou, Xuanjing; Yaromina, Ala; Dörfler, Annegret; Eicheler, Wolfgang; Baumann, Michaël

doi:10.1016/j.radonc.2007.04.014

Cited by 48 publications

(27 citation statements)

References 45 publications

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“…Currently, tumor response in many of clinical studies is determined by volume-related endpoints, such as tumor regression or growth delay, that may not always correlate with local tumor control (34,35). The relative frequency of CSC is highly variable between different tumor types, and even among tumors of the same clinical entity, ranging from a very small population (<1%) as in acute myeloid leukemia or pancreatic cancer, up to 20% to 40% as in some brain, bladder, colorectal cancer, and melanoma.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, therapies that eradicate tumor-initiating cells may not always result in tumor shrinkage (36). On the other hand, common anticancer therapies, including chemotherapy and radiotherapy, eradicate the bulk of tumor cells and lead to decrease in tumor volume but not always targeting the entire CSC population (34,35,37,38). Prediction of the probability of successful treatment is of high importance for the individualization of prostate cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

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Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells

et al. 2015

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Radiotherapy is a curative treatment option in prostate cancer. Nevertheless, patients with high-risk prostate cancer are prone to relapse. Identification of the predictive biomarkers and molecular mechanisms of radioresistance bears promise to improve cancer therapies. In this study, we show that aldehyde dehydrogenase (ALDH) activity is indicative of radioresistant prostate progenitor cells with an enhanced DNA repair capacity and activation of epithelial-mesenchymal transition (EMT

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells

et al. 2015

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“…Although tumors in KP FRT VAtm fl/fl mice were also sensitized to irradiation with 10 fractions of 3 Gy, it is possible that endothelial cell death may increase tumor hypoxia and thereby decrease the efficacy of subsequent fractions of radiation therapy. Furthermore, an increase in growth delay after radiation therapy does not necessarily translate into improved local control (57)(58)(59). To define the contribution of endothelial cells to local control after radiation therapy in this system, future experiments will be required with sarcomas in KP FRT VAtm fl/+ and KP FRT VAtm fl/fl mice using higher doses of radiation and local control as the endpoint.…”

Section: Vatmmentioning

confidence: 99%

Atm deletion with dual recombinase technology preferentially radiosensitizes tumor endothelium

Moding¹,

Lee²,

Castle³

et al. 2014

J. Clin. Invest.

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“…In the present study, the role of EGFR was examined in the Eca109 ESCC cell line, in which EGFR is highly expressed. Overexpression or mutation of EGFR is one of the main mechanisms underlying tumor cell resistance to radiotherapy, which results in poor prognosis (13). Akimoto et al (5) demonstrated that the expression of EGFR and radiosensitivity of solid tumors was negatively correlated, in in vitro experiments.…”

Section: Discussionmentioning

confidence: 99%

“…Akimoto et al (5) demonstrated that the expression of EGFR and radiosensitivity of solid tumors was negatively correlated, in in vitro experiments. Tumors expressing high levels of EGFR were more resistant to radiation compared with tumors expressing low levels of EGFR (13). Therefore, EGFR may represent an effective target for radiosensitization.…”

Section: Discussionmentioning

confidence: 99%

RNA interference for epidermal growth factor receptor enhances the radiosensitivity of esophageal squamous cell carcinoma cell line Eca109

Zhang

Cheng

et al. 2015

Oncology Letters

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Abstract. The present study investigated the effects of small interfering RNAs (siRNAs) specific to the epidermal growth factor receptor (EGFR) gene, on the radiosensitivity of esophageal squamous cell carcinoma cells. EGFR gene siRNAs (EGFR-siRNA) were introduced into esophageal cancer Eca109 cells using Lipofectamine ® 2000. The EGFR messenger (m)RNA expression levels, EGFR protein expression and cell growth were assessed using reverse transcription-polymerase chain reaction analysis, western blot analysis and a Cell Counting Kit-8 (CCK-8), respectively. In addition, colony assays were used to determine the inhibitory effects of X-ray radiation on EGFR-silenced cells. EGFR mRNA and protein levels were reduced in the Eca109 cells transfected with EGFR-siRNA. The relative EGFR mRNA expression levels were reduced to 26.74, 9.52 and 4.61% in Eca109 cells transfected with EGFR-siRNA1, 2 and 3, respectively. These mRNA levels were significantly reduced compared with the those of the control group (42.44%; P<0.0001). Transfection with siRNA3 resulted in the greatest reduction in EGFR mRNA expression, with an inhibition rate of 85%. The relative EGFR protein expression levels were reduced to 24.05, 34.91 and 34.14% in Eca109 cells transfected with EGFR-siRNA1, 2 and 3, respectively. These protein levels were significantly reduced compared with those of the control group (78.57%; P<0.0001). Transfection with siRNA1 resulted in the greatest reduction in EGFR protein expression, with an inhibition rate of 72.84%. This reduction in EGFR expression inhibited the proliferation of Eca109 cells, which was identified using the CCK-8 assay. The proliferation inhibition ratio was 28.2%. The cells treated with irradiation in addition to EGFR-siRNA, demonstrated reduced radiobiological parameters (D0, Dq and SF2) compared with those of cells treated with irradiation only, with a sensitization enhancing ratio of 1.5. In conclusion, suppression of EGFR expression may enhance the radiosensitivity of esophageal cancer Eca109 cells and therefore may represent a promising approach for future clinical practice.

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EGFR-TK inhibition before radiotherapy reduces tumour volume but does not improve local control: Differential response of cancer stem cells and nontumourigenic cells?

Cited by 48 publications

References 45 publications

Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells

Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells

Atm deletion with dual recombinase technology preferentially radiosensitizes tumor endothelium

RNA interference for epidermal growth factor receptor enhances the radiosensitivity of esophageal squamous cell carcinoma cell line Eca109

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