Gαq 突变性葡萄膜黑色素瘤的治疗逃逸：是黏着斑激酶（FAK）在作祟。
Therapeutic Escape in Gαq-mutant Uveal Melanoma: It's a FAK.
机构信息
Bascom Palmer Eye Institute, Sylvester Comprehensive Cancer Center, and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
出版信息
Clin Cancer Res. 2021 Jun 1;27(11):2967-2969. doi: 10.1158/1078-0432.CCR-21-0567. Epub 2021 Mar 25.
Abstract
Through a synthetic lethal screen, ERK activation was found to mediate resistance to FAK inhibition in GNAQ-mutant uveal melanoma. With PLCB-PKC-ERK and Trio-FAK-Yap representing compensatory effectors of mutant Gαq signaling, combined inhibition of both pathways may be a promising therapeutic strategy in metastatic uveal melanoma..
摘要
通过合成致死筛选，发现 ERK 激活介导了对 GNAQ 突变性葡萄膜黑素瘤中 FAK 抑制的耐药性。PLCβ-PKC-ERK 和 Trio-FAK-Yap 代表突变型 Gαq 信号的补偿效应物，联合抑制这两条通路可能是转移性葡萄膜黑素瘤的一种有前途的治疗策略。
相似文献
1
Therapeutic Escape in Gαq-mutant Uveal Melanoma: It's a FAK.Gαq 突变性葡萄膜黑色素瘤的治疗逃逸：是黏着斑激酶（FAK）在作祟。
Clin Cancer Res. 2021 Jun 1;27(11):2967-2969. doi: 10.1158/1078-0432.CCR-21-0567. Epub 2021 Mar 25.
2
Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy for -Driven Uveal Melanoma.合成致死筛选揭示了 FAK 和 MEK 的共靶向作用，作为一种针对 -Driven 葡萄膜黑色素瘤的多模式精准治疗。
Clin Cancer Res. 2021 Jun 1;27(11):3190-3200. doi: 10.1158/1078-0432.CCR-20-3363. Epub 2021 Feb 10.
3
Research in practice: Therapeutic targeting of oncogenic GNAQ mutations in uveal melanoma.临床研究：眼葡萄膜黑素瘤致癌性 GNAQ 突变的治疗靶向。
J Dtsch Dermatol Ges. 2020 Nov;18(11):1245-1248. doi: 10.1111/ddg.14288. Epub 2020 Sep 21.
4
Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry.GNAQ 葡萄膜黑素瘤癌基因通过 trio 调控的 rho GTP 酶信号通路非 Hippo 依赖性激活 YAP。
Cancer Cell. 2014 Jun 16;25(6):831-45. doi: 10.1016/j.ccr.2014.04.016. Epub 2014 May 29.
5
Combined Inhibition of Gα and MEK Enhances Therapeutic Efficacy in Uveal Melanoma.联合抑制 Gα 和 MEK 可增强葡萄膜黑色素瘤的治疗效果。
Clin Cancer Res. 2021 Mar 1;27(5):1476-1490. doi: 10.1158/1078-0432.CCR-20-2860. Epub 2020 Nov 23.
6
Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner.联合使用小分子 MEK 和 PI3K 抑制剂可增强依赖突变 GNAQ 和 GNA11 的葡萄膜黑色素瘤细胞死亡。
Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
7
High-throughput chemogenetic drug screening reveals PKC-RhoA/PKN as a targetable signaling vulnerability in GNAQ-driven uveal melanoma.高通量化学遗传学药物筛选揭示 PKC-RhoA/ PKN 是 GNAQ 驱动的葡萄膜黑素瘤中可靶向的信号脆弱性靶点。
Cell Rep Med. 2023 Nov 21;4(11):101244. doi: 10.1016/j.xcrm.2023.101244. Epub 2023 Oct 18.
8
A Platform of Synthetic Lethal Gene Interaction Networks Reveals that the GNAQ Uveal Melanoma Oncogene Controls the Hippo Pathway through FAK.合成致死基因互作网络平台揭示 GNAQ 葡萄膜黑素瘤癌基因通过 FAK 调控 Hippo 通路
Cancer Cell. 2019 Mar 18;35(3):457-472.e5. doi: 10.1016/j.ccell.2019.01.009. Epub 2019 Feb 14.
9
Protein kinase C inhibitor AEB071 targets ocular melanoma harboring GNAQ mutations via effects on the PKC/Erk1/2 and PKC/NF-κB pathways.蛋白激酶 C 抑制剂 AEB071 通过影响 PKC/Erk1/2 和 PKC/NF-κB 通路靶向携带 GNAQ 突变的眼黑素瘤。
Mol Cancer Ther. 2012 Sep;11(9):1905-14. doi: 10.1158/1535-7163.MCT-12-0121. Epub 2012 May 31.
10
Chloroquine Sensitizes -mutated Melanoma to MEK1/2 Inhibition.氯喹使 -mutated 黑色素瘤对 MEK1/2 抑制敏感。
Clin Cancer Res. 2020 Dec 1;26(23):6374-6386. doi: 10.1158/1078-0432.CCR-20-1675. Epub 2020 Sep 15.
引用本文的文献
1
Low Level of PALMD Contributes to the Metastasis of Uveal Melanoma.PAK 相关局部黏附激酶（PALMD）水平低促进葡萄膜黑色素瘤转移。
Front Oncol. 2022 Apr 13;12:802941. doi: 10.3389/fonc.2022.802941. eCollection 2022.
本文引用的文献
1
Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy for -Driven Uveal Melanoma.合成致死筛选揭示了 FAK 和 MEK 的共靶向作用，作为一种针对 -Driven 葡萄膜黑色素瘤的多模式精准治疗。
Clin Cancer Res. 2021 Jun 1;27(11):3190-3200. doi: 10.1158/1078-0432.CCR-20-3363. Epub 2021 Feb 10.
2
HDAC Inhibition Enhances the Efficacy of MEK Inhibitor Therapy in Uveal Melanoma.组蛋白去乙酰化酶抑制增强 MEK 抑制剂治疗葡萄膜黑色素瘤的疗效。
Clin Cancer Res. 2019 Sep 15;25(18):5686-5701. doi: 10.1158/1078-0432.CCR-18-3382. Epub 2019 Jun 21.
3
Punctuated evolution of canonical genomic aberrations in uveal melanoma.葡萄膜黑色素瘤中典型基因组畸变的间断性进化
Nat Commun. 2018 Jan 9;9(1):116. doi: 10.1038/s41467-017-02428-w.
4
Dysregulated GPCR Signaling and Therapeutic Options in Uveal Melanoma.葡萄膜黑色素瘤中G蛋白偶联受体信号失调与治疗选择
Mol Cancer Res. 2017 May;15(5):501-506. doi: 10.1158/1541-7786.MCR-17-0007. Epub 2017 Feb 21.
5
Frequent mutation of BAP1 in metastasizing uveal melanomas.转移性葡萄膜黑色素瘤中 BAP1 的频繁突变。
Science. 2010 Dec 3;330(6009):1410-3. doi: 10.1126/science.1194472. Epub 2010 Nov 4.
Zotero 插件