EGFR gene amplification is related to adverse clinical outcomes in cervical squamous cell carcinoma, making the EGFR pathway a novel therapeutic target

Iida, Kouji; Nakayama, Kentaro; Rahman, Munmun; Ishikawa, Masatoshi; Katagiri, Atsuko; Yeasmin, Sabina; Otsuki, Yoshiro; Kobayashi, Hiroshi; Nakayama, Shinichi; Miyazaki, Kohji

doi:10.1038/bjc.2011.222

Cited by 65 publications

(59 citation statements)

References 40 publications

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“…EGFR is also known as the HER (Human Epidermal factor Receptor) receptor and is a target for treatment. EGFR/HER family inhibitors, such as gefitinib, erlotinib, cetuximab, lapatinib, trastuzumab, panitumumab, are being evaluated in cervical cancer and are reviewed in depth (Lida et al, 2011;Soonthornthum et al, 2013;Vici et al, 2014). Most of these are injectables (subcutaneous, intramuscular or intravenous), whilst some like erlotinib, are available as oral tablets.…”

Section: Egfrmentioning

confidence: 99%

Role of Cytokines in Genesis, Progression and Prognosis of Cervical Cancer

Paradkar¹,

Joshi²,

Mertia³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Cytokine research is currently at the forefront in cancer research. Deciphering the functions of these multiple small molecules, discovered within the cell and in intercellular spaces, with their abundance and pleotrophism, was initially a great challenge. Advances in analytical chemistry and molecular biology have made it possible to unravel the pathophysiological functions of these polypeptides/proteins which are called interleukins, chemokines, monokines, lymphokines and growth factors. With more than 5 million women contracting cervical cancer every year this cancer is a major cause of mortality and morbidity the world over, particularly in the developing countries. In more than 95% of cases it is associated with human papilloma virus (HPV) infection which is persistent, particularly in those with a defective immune system. Although preventable, the mere magnitude of prevalence of HPV in the world population makes it a dominating current health hazard. The discovery of cytokine dysregulation in cervical cancer has spurted investigation into the possibility of using them as biomarkers in the early diagnosis of cases at high risk of developing cancer. Their critical role in carcinogenesis and progression of cervical cancer is now being revealed to a great extent. From diagnostics to prognosis, and now with a possible role in therapeutics and prevention of cervical cancer, the cytokines are being evaluated in all anticancer approaches. This review endeavours to capture the essence of the astonishing journey of cytokine research in cervical neoplasia.

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Section: Egfrmentioning

confidence: 99%

Role of Cytokines in Genesis, Progression and Prognosis of Cervical Cancer

Paradkar¹,

Joshi²,

Mertia³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…In addition, previous studies identified that the frequencies of NRAS, HRAS and BRAF hotspot mutations were absent or low in cervical squamous cell carcinoma or adenosquamous carcinoma (11,21,25,26). Similarly, the current study also did not identify the potential hotspot mutations in these genes in the 260 cases of cervical carcinoma with distinct subtypes.…”

Section: Discussionmentioning

confidence: 41%

Mutational analysis of the RAS/RAF/MEK/ERK signaling pathway in 260 Han Chinese patients with cervical carcinoma

Zou

Liu

et al. 2017

Oncology Letters

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Abstract. Prevalent mutations in the mitogen-activated protein kinase 1 (MAPK1)/extracellular signal-regulated kinase 2 (ERK2) pathway have been identified in cervical squamous cell carcinoma in a large-scale genome sequencing effort. Furthermore, mutations in the rat sarcoma viral oncogene homolog (RAS)/Raf/Mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway have also been revealed to have important roles in the pathogenesis of human cancer. However, whether the potential hotspot mutations in ERK2 and other components of the RAS/RAF/MEK/ERK signaling pathway also exist in Chinese patients with cervical carcinoma remains to be elucidated. In the present study, a total of 260 patients with cervical carcinoma of distinct subtypes were analyzed for the presence of potential hotspot mutations in the RAS/RAF/MEK/ERK signaling pathway. No ERK2 mutations were detected in these samples; however, Kirsten RAS (KRAS) p.G12D (c.35G>A) mutation was identified in 2/26 (7.7%) cervical adenocarcinoma cases, including 1/20 cervical mucinous adenocarcinoma and 1/6 cervical endometrioid carcinoma cases. In addition, no mutations in the ERK1, neuroblastoma RAS, Harvey RAS or B-Raf proto-oncogene serine/threonine kinase genes were detected in the present study. These results indicated that ethnic differences may be a primary reason for the discrepancy in ERK2 mutation frequencies between the current study and previous studies. Furthermore, mutation in the KRAS gene, but not other genes in the RAS/RAF/MEK/ERK signaling pathway, may have an active role in the pathogenesis of cervical carcinoma. IntroductionCervical carcinoma is the second most frequent type of gynecological malignancy (1). Despite the availability of Pap smear-based screening decreasing the incidence and mortality of cervical carcinoma, it remains a primary cause of cancer-associated mortality in females globally (2). It is well established that human papillomavirus infection has an important role in the development of cervical carcinoma, in addition to genetic alterations that have also been demonstrated to be required for the initiation and progression of this malignancy (3). Although there have been developments in the understanding of the molecular etiology of cervical carcinoma, the underlying mechanistic details remain to be elucidated, emphasizing the requirement for identifying novel molecular genetic alterations.The RAS/RAF/MEK/ERK cascade is an important signaling pathway that regulates diverse cellular functions, including cell proliferation, survival, differentiation and migration (4). A number of previous studies have demonstrated that mutations in the kinases of the RAS/RAF/MEK/ERK transduction pathway are frequently observed in human cancer, including cervical carcinoma (5-8). Of these, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS p.G12, p.G13 and p.Q61), neuroblastoma RAS (NRAS; p.G12, p.G13 and p.Q61), Harvey RAS (HRAS; p.G12, p.G13 and p.Q61) and B-Raf proto-oncogene serine/threoni...

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“…Согласно результатам, полученным Li и соавт., увеличение числа копий EGFR-гена может быть причиной примерно трети случаев гиперэкспрессии рецептора при ЦИН2/3 и РШМ [59], следовательно, это не единственный механизм, реализуемый in vivo. Схожие результаты получены и другими авторами [60,61].…”

Section: факторы роста: эпидермальный фактор роста (Egf) и его рецептunclassified

Remodeling of angiogenesis and lymphangiogenesis in cervical cancer development

et al. 2015

BIOMED KHIM

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Ability to stimulate angiogenesis/lymphangiogenesis is recognized as an inherent feature of cancer cells providing necessary conditions for their growth and dissemination. “Angiogenic switch” is one of the earliest consequences of malignant transformation that encompasses a great number of genes and triggers a complex set of signaling cascades in endothelial cells. The processes of tumor microvasculature development are closely connected to the steps of carcinogenesis (from benign lesions to invasive forms) and occur through multiple deviations from the norm. Analysis of expression of proangiogenic factors at successive steps of cervical cancer development (intraepithelial neoplasia, cancer in situ, microinvasive, and invasive cancer) enables to reconstruct the regulatory mechanisms of (lymph-)angiogenesis and to discriminate the most important components. This review presents detailed analysis of literature data on expression of the key regulators of angiogenesis in cervical intraepithelial neoplasia and cervical cancer. Their possible involvement in molecular mechanisms of neoplastic transformation of epithelial cells, as well as invasion and tumor metastasis is discussed. Correlation between expression of proangiogenic molecular factors and various clinicopathological parameters is considered, the potential of their use in molecular diagnostics and targeted therapy of cervical cancer is reviewed. Particular attention is paid to relatively poorly studied regulators of lymphangiogenesis and “non-VEGF dependent”, or alternative, angiogenic pathways that constitute the prospect of future research in the field.

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EGFR gene amplification is related to adverse clinical outcomes in cervical squamous cell carcinoma, making the EGFR pathway a novel therapeutic target

Cited by 65 publications

References 40 publications

Role of Cytokines in Genesis, Progression and Prognosis of Cervical Cancer

Role of Cytokines in Genesis, Progression and Prognosis of Cervical Cancer

Mutational analysis of the RAS/RAF/MEK/ERK signaling pathway in 260 Han Chinese patients with cervical carcinoma

Remodeling of angiogenesis and lymphangiogenesis in cervical cancer development

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