Dual inhibition of epidermal growth factor receptor and insulin-like growth factor receptor I: reduction of angiogenesis and tumor growth in cutaneous squamous cell carcinoma.
Dual inhibition of epidermal growth factor receptor and insulin-like growth factor receptor I: reduction of angiogenesis and tumor growth in cutaneous squamous cell carcinoma.
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DOI：
10.1002/hed.21419
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发表时间：
2011-02
影响因子：
2.9
通讯作者：
Myers, Jeffrey N.
中科院分区：
文献类型：
--
作者：
Galer, Chad E.;Corey, Christina L.;Wang, Zhuoying;Younes, Maher N.;Gomez-Rivera, Fernando;Jasser, Samar A.;Ludwig, Dale L.;El-Naggar, Adel K.;Weber, Randal S.;Myers, Jeffrey N.
关键词：
皮肤鳞状细胞癌（CSCC）是第二常见的非黑色素瘤皮肤癌。在美国每年发生的约250，000例病例中，大多数是小的，非侵袭性的，仅通过切除治愈。然而，这些肿瘤的一个子集，其定义为低分化组织学，大肿瘤大小，邻近结构的侵袭和/或区域转移，可以证明耐治疗，尽管辅助放疗，复发和淋巴结转移的风险增加。新的治疗方法对于改善侵袭性CSCC患者的预后是必要的。我们分析了靶向治疗对CSCC细胞系的生长和存活的影响，使用抗IGF-IR抗体A12，单独或与抗EGF-R抗体西妥昔单抗组合，在体外和体内在CSCC的无胸腺裸鼠模型中。A12和西妥昔单抗抑制IGF-IR和EGFR信号通路，抑制SCC细胞系的增殖并诱导其凋亡。免疫组化染色显示，治疗的肿瘤异种移植物中增殖细胞核抗原（PCNA）和微血管密度（MVD）降低，细胞凋亡增加。此外，单独或与西妥昔单抗组合施用A12分别抑制肿瘤生长51%和92%，并显著提高CSCC裸鼠模型中的存活率（分别为p = 0.044和p < 0.001）。这些数据表明，EGFR和IGF-IR的单克隆抗体的双重治疗可能在治疗CSCC的治疗上是有用的。
Cutaneous squamous cell carcinoma (CSCC) is the second most common non-melanoma skin cancer. The majority of the ~250,000 cases occurring annually in the United States are small, non-aggressive, and cured by excision alone. However, a subset of these tumors which are defined by poorly differentiated histology, large tumor size, invasion of adjacent structures and/or regional metastases can prove resistant to treatment despite adjuvant radiotherapy and have increased risk of recurrence and nodal metastasis. Novel therapeutic approaches are necessary to improve outcomes for patients with aggressive CSCC. We analyzed the effect of targeted therapy on the growth and survival of CSCC cell lines using an anti-IGF-IR antibody, A12, alone or in combination with an anti-EGF-R antibody, cetuximab, both in vitro and in vivo in an athymic nude mouse model of CSCC. Treatment with A12 and cetuximab inhibited the signaling pathways of IGF-IR and EGFR and inhibited proliferation and induced apoptosis of SCC cell lines in vitro. Immunohistochemical staining revealed decreased proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) as well as increased apoptosis within the treated tumor xenografts. In addition, the administration of A12, alone or in combination with cetuximab inhibited the growth of tumors by 51% and 92% respectively, and significantly enhanced survival in the nude mouse model of CSCC (p = 0.044 and p < 0.001 respectively). These data suggest that dual treatment with monoclonal antibodies to the EGFR and IGF-IR may be therapeutically useful in the treatment of CSCC.
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影响因子：
7.4
作者：
Camirand, A;Zakikhani, M;Young, F;Pollak, M
通讯作者：
Pollak, M
影响因子：
10.3
作者：
de Vries, E;van de Poll-Franse, LV;Coebergh, JWW
通讯作者：
Coebergh, JWW
影响因子：
3.9
作者：
Belfiore, A;Pandini, G;Vigneri, R
通讯作者：
Vigneri, R
影响因子：
3.3
作者：
GOLDMAN, CK;KIM, J;GILLESPIE, GY
通讯作者：
GILLESPIE, GY
影响因子：
254.7
作者：
Jemal, A;Murray, T;Thun, MJ
通讯作者：
Thun, MJ