Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) negatively affect overall survival in carcinoma of the cervix treated with radiotherapy

Gaffney, David K.; Haslam, D; Tsodikov, Alexander; Hammond, Elizabeth H.; Seaman, James P.; Holden, Joseph A.; Lee, R.Jeffrey; Zempolich, Karen; Dodson, Mark K.

doi:10.1016/s0360-3016(03)00209-8

Cited by 111 publications

(78 citation statements)

References 19 publications

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“…Previous studies have shown that EGFR expression decreased radiosensitivity of cervical cancer (7)(8)(9). Moreover, inhibition of EGFR with cetuximab plus radiotherapy increased overall survival when compared with the use of radiotherapy alone (10).…”

Section: Introductionmentioning

confidence: 96%

Metadherin regulates radioresistance in cervical cancer cells

et al. 2012

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Abstract. Metadherin (MTDH) promotes cancer metastasis, chemoresistance, invasion and angiogenesis. Upregulation of MTDH is correlated with both progression and poor clinical outcome of many types of cancers; however, there is currently no information regarding the role of MTDH in radiation sensitivity. Here, we investigated the effects of MTDH on the radiosensitivity of cervical cancer cells using the SiHa cell line. We discovered that cervical cancer cells in which MTDH was knocked down had significantly increased radiosensitivity as measured by a clonogenic assay. MTDH knockdown cells also had increased apoptosis and a decreased proportion of cells arrested in the G2 phase after radiation treatment. MTDH knockdown also weakened the repair of DNA double-strand breaks (DSBs) induced by radiation. These results indicate that MTDH affects the radiosensitivity of cervical cancer cells and that MTDH may be a novel target to improve cervical cancer radiation response.

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Section: Introductionmentioning

confidence: 96%

Metadherin regulates radioresistance in cervical cancer cells

et al. 2012

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“…Changes in 52 conductor genes determine the biological behavior of squamous neoplasms, including EGFR, VEGF, hypoxia‐inducible factor (HIF), HYAL2, SV2A, and CASP10 25, 26. Furthermore, the overexpression of VEGF in radiotherapy‐treated IB2 and IVA tumors negatively influenced OS 27. Our study suggests that VEGF overexpression negatively affects survival, even after controlling for factors such as tumor size, histological grade, and local extension of pathology.…”

Section: Discussionmentioning

confidence: 74%

“…Research suggests that EGFR is altered in more than 80% of CC patients, and have been associated with poor prognosis due to its role in chemo and radiotherapy responses 27. Liang and colleagues demonstrated that teletherapy increased receptor bioavailability and outsourcing; thus, blocking the receptor could explain the increased response in CC patients specifically treated with EGFR‐targeted drugs 28.…”

Section: Discussionmentioning

confidence: 99%

Epithelial–mesenchymal transition, proliferation, and angiogenesis in locally advanced cervical cancer treated with chemoradiotherapy

Rojas‐Puentes

Cardona²,

Carranza³

et al. 2016

Cancer Medicine

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We evaluated the association between epithelial–mesenchymal transition (EMT)‐derived markers and expression of proteins associated with cell proliferation and tumor growth, as well as their prognostic roles, in 61 patients (mean age 52 ± 10 years) with locally advanced cervical cancer, all of whom were treated with chemoradiation and intracavitary brachytherapy. We used immunohistochemical analysis to assess the expression of proteins targeted in our investigation. Various statistical analyses were then conducted to assess protein marker associations with survival outcomes. Forty‐six percent of the patients were positive for human papilloma virus. Median progression‐free survival (PFS) was 6.6 months (95% confidence interval [CI]: 4.0–9.1, whereas overall survival (OS) was 30.0 months (95% CI: 11–48). Multivariate analysis demonstrated that vascular endothelial growth factor (VEGF) (P = 0.002), epidermal growth factor receptor (EGFR) (P = 0.001), and TWIST2 (P = 0.001) expression levels, as well as a tumor size <6 cm (P = 0.02), influenced OS. Changes in TWIST2 levels and loss of E‐cadherin expression were correlated with VEGF and EGFR levels; furthermore, patients with high TWIST2 expression had shorter OS (P = 0.0001), as those with loss of E‐cadherin (P = 0.02). OS was even shorter when positive EGFR or VEGF expression was related with EMT markers (positive EGFR + negative E‐cadherin: median 14 months, 95% CI: 3–24; negative EGFR + positive E‐cadherin: median 31 months, 95% CI: 14–NA; P = 0.02.). The presence of EMT markers was associated with proliferative and pro‐angiogenic protein expression and influenced the prognosis of locally advanced cervical cancer.

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“…[1][2][3][4][5][6] It is shown in several studies that high levels of EGFR amplification and overexpression are present in cervical cancer. [7][8][9][10] One of the specific signal tranduction pathways, phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated by stimulation of EGFR family via certain growth factors and cytokines. [11][12][13] Akt is a protein kinase first identified in 1991 and it regulates cell survival.…”

Section: Introductionmentioning

confidence: 99%

The Prognostic and Predictive Value of Expression of P-AKT in Patients with FIGO IIB Locally Advanced Cervical Cancer under Chemotherapy.

Koçak¹,

Barışık²,

Mayadağlı³

et al. 2013

UHOD

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To evaluate the relation between expression of P-Akt and radiotherapy response, disease-free survival and overall survival in cervical cancer patients. A total of 50 patients with FIGO stage IIB locally advanced squamous cell cervical cancer treated primarily with chemoradiotherapy were included in the present study. All patients received external beam radiotherapy (EBRT; 46-50.4 Gy with 1.8-2 Gy of daily fraction, five times a week) followed by high-dose rate brachytherapy (HDR 26 Gy at point A, with 6.5 Gy per fraction a week for 4 weeks). Chemotherapy consisted of 40 mg/m2 cisplatin i.v. once a week for 5 weeks concomitant with external pelvic radiation. Paraffin-embedded, formalin-fixed primary tumor tissue was collected from each patient to identify P-Akt expression, retrospectively. The median follow up time for the study population was 30 (12-120) months. Expression of P-Akt was identified in 86% (43/50) of patients. Overall 3-years survival and disease free survival were 89.3% and 79% ; respectively in the study population. There was no significant association between P-Akt staining and survival (89% vs 85.7%, p= 0.641) and disease-free survival (80% vs 88.2%, p= 0.498). There was no relation between expression of P-Akt and treatment response, size of the tumor, lymph node status, age, local and distant failures. Univariate analysis revealed significantly reduced overall 3-years survival and disease free survival only for patients with poor treatment response (p= 0.001). In multivariate analysis, treatment response was found to be statistically significant parameter only for DFS ( p= 0.001 ). In conclusion, in our study, expression of P-Akt was detected in majority of cervical cancer patients. However no correlation was observed between P-Akt staining degree and treatment response Keywords: P-Akt expression, Cervical cancer, Chemoradiotherapy, Radiation response ÖZET Kemoradyoterapi Uygulanan FIGO IIB Lokal ‹leri Servikal Kanserli Hastalarda P-AKT Ekspresyonunun Prediktif ve Prognostik De¤eriServiks kanserli hastalarda, P-Akt ekspresyonu ile radyoterapi cevab›, hastal›ks›z sa¤kal›m ve tüm sa¤kal›m aras›ndaki iliflkiyi de¤erlendirmek. Bu çal›flmaya, primer kemoradyoterapi ile tedavi edilen, FIGO IIB lokal ileri skuamoz hücreli serviks kanserli 50 olgu dahil edildi. Tüm hastalar eksternal radyoterapi (EBRT; 46-50.4 Gy, günlük fraksiyon 1.8-2 Gy , haftada 5 gün) ve takiben yüksek doz oranl› brakiterapi (A noktas›na 26 Gy, fraksiyon dozu 6.5 Gy,haftada bir, 4 hafta boyunca) ald›lar. Kemoterapi eksternal pelvik radyoterapi ile efl zamanl› haftada bir 40 mg/m2 cisplatin olarak uyguland›. Her hastan›n formalinle fikse edilmifl parafin bloklar› toplanarak retrospektif olarak P-Akt ekspresyonuna bak›ld›. Boyanma 0 dan 3'e kadar skorland›.

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Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) negatively affect overall survival in carcinoma of the cervix treated with radiotherapy

Cited by 111 publications

References 19 publications

Metadherin regulates radioresistance in cervical cancer cells

Metadherin regulates radioresistance in cervical cancer cells

Epithelial–mesenchymal transition, proliferation, and angiogenesis in locally advanced cervical cancer treated with chemoradiotherapy

The Prognostic and Predictive Value of Expression of P-AKT in Patients with FIGO IIB Locally Advanced Cervical Cancer under Chemotherapy.

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