Overexpression of epidermal growth factor type-1 receptor (EGF-R1) in cervical cancer: Implications for Cetuximab-mediated therapy in recurrent/metastatic disease

Bellone, Stefania; Frera, Gianluca; Landolfi, Gianpiero; Romani, Chiara; Bandiera, Elisabetta; Tognon, Germana; Román, Juan José Mora; Burnett, Alexander; Pecorelli, Sërgio; Santin, Alessandro D.

doi:10.1016/j.ygyno.2007.04.028

Cited by 81 publications

(44 citation statements)

References 40 publications

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“…bellone et al found that 14 out of 14 (100%) primary cervical cancer cell lines from cervical biopsies and recurrent sites of disease, as well as 7 out of 8 (87.5%) established cervical cancer cell lines expressed epidermal growth factor receptor-1 (136). minimal complement-dependent cytotoxicity was detected in the majority of cell lines exposed to complement ± cetuximab in the absence of peripheral blood lymphocytes.…”

Section: Distant Recurrence or Loco-regional Recurrence Not Amenable mentioning

confidence: 99%

Treatment options in recurrent cervical cancer (Review)

Gadducci¹,

Tana²,

Cosio³

et al. 2010

Oncology Letters

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Abstract. the management of recurrent cervical cancer depends mainly on previous treatment and on the site and extent of recurrence. concurrent cisplatin-based chemoradiation is the treatment of choice for patients with pelvic failure after radical hysterectomy alone. However, the safe delivery of high doses of radiotherapy is much more difficult in this clinical setting compared with primary radiotherapy. Pelvic exenteration usually represents the only therapeutic approach with curative intent for women with central pelvic relapse who have previously received irradiation. In a recent series, the 5-year overall survival and operative mortality after pelvic exenteration ranged from 21 to 61% and from 1 to 10%, respectively. Free surgical margins, negative lymph nodes, small tumour size and long disease-free interval were associated with a more favourable prognosis. currently, pelvic reconstructive procedures (continent urinary conduit, low colorectal anastomosis, vaginal reconstruction with myocutaneous flaps) are strongly recommended after exenteration. concurrent cisplatin-based chemo-radiation is the treatment of choice for isolated para-aortic lymph node failure, with satisfactory chances of a cure in asymptomatic patients. chemotherapy is administered with palliative intent to women with distant or loco-regional recurrences not amenable by surgery or radiotherapy. cisplatin is the most widely used drug, with a response rate of 17-38% and a median overall survival of 6.1-7.1 months. cisplatin-based combination chemotherapy achieves higher response rates (22-68%) when compared with single-agent cisplatin, but median overall survival is usually less than one year. In a recent gynecologic Oncology Group (GOG) trial the combination topotecan + cisplatin obtained a significantly longer overall survival than single-agent cisplatin in patients with metastatic or recurrent or persistent cervical cancer. A subsequent gog study showed a trend in terms of longer overall survival and better quality of life for the doublet cisplatin + paclitaxel vs. the doublets cisplatin + topotecan, cisplatin + vinorelbine, and cisplatin + gemcitabine. Molecularly targeted therapy may represent a novel therapeutic tool, but its use alone or in combination with chemotherapy is still investigational.

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Section: Distant Recurrence or Loco-regional Recurrence Not Amenable mentioning

confidence: 99%

Treatment options in recurrent cervical cancer (Review)

Gadducci¹,

Tana²,

Cosio³

et al. 2010

Oncology Letters

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“…In fact, preclinical studies of cetuximab (Erbitux), a chimeric monoclonal antibody against EGFR, produced significant inhibition (range, 37%-58%) in all EGFR-positive cervical cancer cell lines tested. 73 A study that combined cetuximab with the combination of cisplatin and topotecan was terminated prematurely because of excessive hematologic, renal, and infectious toxicity. 74 Previous treatment and poor performance status of the patients may have contributed to those toxicities, but a pharmacokinetic or pharmacodynamic interaction cannot be excluded.…”

Section: Review Article 3172mentioning

confidence: 99%

Novel chemotherapy approaches for cervical cancer

Movva

Rodriguez

Arias-Pulido

et al. 2009

Cancer

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Cancer of the cervix is the second most common malignancy among women worldwide. The last 20 years have lead to numerous advances in the medical management of locally advanced cervical cancer, including preventive vaccination, chemoradiation, and neoadjuvant chemotherapy. The treatment of metastatic disease is palliative at best. Platinum‐based chemotherapy remains the standard of care for inoperable patients who have recurrent disease. However, because most patients initially receive concomitant platinum‐based therapy with radiation, many recurrent tumors are refractory to platinum. The use of novel therapeutic approaches targeted to the carcinogenic processes that leads to the ontogenesis of cervical cancer should be promoted in clinical studies to improve patient outcomes. Cancer 2009; 115:3166–80. © 2009 American Cancer Society.

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“…In the adult, all four receptors are widely expressed at low levels. However, overexpression of ErbB1 and/or ErbB2 was implicated in the pathogenesis of many carcinomas, including those derived from head and neck (4,5), breast (6,7), lung (8), gastrointestinal tract (4,9), prostate (10,11), gynecologic tract (12,13) and pancreas (14). Aberrant ErbB signaling promotes resistance to commonly used therapeutic modalities, including hormonal agents (15), chemotherapy (16) and radiotherapy (17).…”

Section: Introductionmentioning

confidence: 99%

Flexible Targeting of ErbB Dimers That Drive Tumorigenesis by Using Genetically Engineered T Cells

Davies

Foster

Stegen

et al. 2012

Mol Med

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Pharmacological targeting of individual ErbB receptors elicits antitumor activity, but is frequently compromised by resistance leading to therapeutic failure. Here, we describe an immunotherapeutic approach that exploits prevalent and fundamental mechanisms by which aberrant upregulation of the ErbB network drives tumorigenesis. A chimeric antigen receptor named T1E28z was engineered, in which the promiscuous ErbB ligand, T1E, is fused to a CD28 + CD3ζ endodomain. Using a panel of ErbBengineered 32D hematopoietic cells, we found that human T1E28z + T cells are selectively activated by all ErbB1-based homodimers and heterodimers and by the potently mitogenic ErbB2/3 heterodimer. Owing to this flexible targeting capability, recognition and destruction of several tumor cell lines was achieved by T1E28z + T cells in vitro, comprising a wide diversity of ErbB receptor profiles and tumor origins. Furthermore, compelling antitumor activity was observed in mice bearing established xenografts, characterized either by ErbB1/2 or ErbB2/3 overexpression and representative of insidious or rapidly progressive tumor types. Together, these findings support the clinical development of a broadly applicable immunotherapeutic approach in which the propensity of solid tumors to dysregulate the extended ErbB network is targeted for therapeutic gain.

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Overexpression of epidermal growth factor type-1 receptor (EGF-R1) in cervical cancer: Implications for Cetuximab-mediated therapy in recurrent/metastatic disease

Cited by 81 publications

References 40 publications

Treatment options in recurrent cervical cancer (Review)

Treatment options in recurrent cervical cancer (Review)

Novel chemotherapy approaches for cervical cancer

Flexible Targeting of ErbB Dimers That Drive Tumorigenesis by Using Genetically Engineered T Cells

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