NOTCH1 Signaling in Head and Neck Squamous Cell Carcinoma.
NOTCH1 Signaling in Head and Neck Squamous Cell Carcinoma.
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头颈部鳞状细胞癌中的NOTCH1信号转导。
DOI：
10.3390/cells9122677
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发表时间：
2020-12-12
期刊：
影响因子：
6
通讯作者：
Frederick MJ
中科院分区：
文献类型：
--
作者：
Shah PA;Huang C;Li Q;Kazi SA;Byers LA;Wang J;Johnson FM;Frederick MJ
对于常见且致命的头颈鳞状细胞癌（HNSCC），缺乏生物标志物驱动的靶向治疗。开发此类疗法的努力受到肿瘤抑制功能丧失主导的基因组景观的阻碍，其中包括在 HNSCC 中频繁突变的 NOTCH1。更清楚地了解 HNSCC 中的 NOTCH1 信号传导对于临床靶向该通路至关重要。 HNSCC 中 NOTCH1 突变的结构特征表明，大多数突变预计会导致功能丧失，这与 NOTCH1 在这种癌症中作为肿瘤抑制因子的作用一致。在含有突变型或野生型 NOTCH1 的 HNSCC 细胞系中对 NOTCH1 信号传导的实验操作进一步支持了肿瘤抑制功能。此外，NOTCH1 信号传导的缺失可能会促进 HNSCC 肿瘤的发生和临床侵袭性。我们最近的数据表明，NOTCH1 控制参与早期分化的基因，这些基因可能会根据癌症的遗传背景产生不同的表型后果，包括获得伪干细胞样特性。 NOTCH1 突变的存在可以预测对免疫检查点或磷脂酰肌醇 3-激酶抑制剂治疗的反应。后者正在临床试验中进行测试，如果得到验证，可能会导致第一个生物标志物驱动的 HNSCC 靶向疗法的开发。
Biomarker-driven targeted therapies are lacking for head and neck squamous cell carcinoma (HNSCC), which is common and lethal. Efforts to develop such therapies are hindered by a genomic landscape dominated by the loss of tumor suppressor function, including NOTCH1 that is frequently mutated in HNSCC. Clearer understanding of NOTCH1 signaling in HNSCCs is crucial to clinically targeting this pathway. Structural characterization of NOTCH1 mutations in HNSCC demonstrates that most are predicted to cause loss of function, in agreement with NOTCH1’s role as a tumor suppressor in this cancer. Experimental manipulation of NOTCH1 signaling in HNSCC cell lines harboring either mutant or wild-type NOTCH1 further supports a tumor suppressor function. Additionally, the loss of NOTCH1 signaling can drive HNSCC tumorigenesis and clinical aggressiveness. Our recent data suggest that NOTCH1 controls genes involved in early differentiation that could have different phenotypic consequences depending on the cancer’s genetic background, including acquisition of pseudo-stem cell-like properties. The presence of NOTCH1 mutations may predict response to treatment with an immune checkpoint or phosphatidylinositol 3-kinase inhibitors. The latter is being tested in a clinical trial, and if validated, it may lead to the development of the first biomarker-driven targeted therapy for HNSCC.
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DOI：
10.1182/asheducation-2009.1.353
发表时间：
2009-01-01
期刊：
Hematology. American Society of Hematology. Education Program
影响因子：
--
作者：
Ferrando, Adolfo A
通讯作者：
Ferrando, Adolfo A
影响因子：
8.8
作者：
Cheng H;Yang X;Si H;Saleh AD;Xiao W;Coupar J;Gollin SM;Ferris RL;Issaeva N;Yarbrough WG;Prince ME;Carey TE;Van Waes C;Chen Z
通讯作者：
Chen Z
影响因子：
8.8
作者：
Campbell JD;Yau C;Bowlby R;Liu Y;Brennan K;Fan H;Taylor AM;Wang C;Walter V;Akbani R;Byers LA;Creighton CJ;Coarfa C;Shih J;Cherniack AD;Gevaert O;Prunello M;Shen H;Anur P;Chen J;Cheng H;Hayes DN;Bullman S;Pedamallu CS;Ojesina AI;Sadeghi S;Mungall KL;Robertson AG;Benz C;Schultz A;Kanchi RS;Gay CM;Hegde A;Diao L;Wang J;Ma W;Sumazin P;Chiu HS;Chen TW;Gunaratne P;Donehower L;Rader JS;Zuna R;Al-Ahmadie H;Lazar AJ;Flores ER;Tsai KY;Zhou JH;Rustgi AK;Drill E;Shen R;Wong CK;Cancer Genome Atlas Research Network;Stuart JM;Laird PW;Hoadley KA;Weinstein JN;Peto M;Pickering CR;Chen Z;Van Waes C
通讯作者：
Van Waes C
影响因子：
28.2
作者：
Agrawal N;Jiao Y;Bettegowda C;Hutfless SM;Wang Y;David S;Cheng Y;Twaddell WS;Latt NL;Shin EJ;Wang LD;Wang L;Yang W;Velculescu VE;Vogelstein B;Papadopoulos N;Kinzler KW;Meltzer SJ
通讯作者：
Meltzer SJ
影响因子：
64.5
作者：
ELLISEN, LW;BIRD, J;SKLAR, J
通讯作者：
SKLAR, J