A Drosophila platform identifies a novel, personalized therapy for a patient with adenoid cystic carcinoma

被引：24

作者：

Bangi, Erdem ^{[1
,9
]}

Smibert, Peter ^{[1
,10
]}

Uzilov, Andrew, V ^{[3
,4
,5
]}

Teague, Alexander G. ^{[1
]}

Gopinath, Sindhura ^{[1
,3
,4
]}

Antipin, Yevgeniy ^{[3
,4
]}

Chen, Rong ^{[3
,4
,5
]}

Hecht, Chana ^{[1
]}

Gruszczynski, Nelson ^{[1
,11
]}

Yon, Wesley J. ^{[1
]}

Malyshev, Denis ^{[1
,12
]}

Laspina, Denise ^{[1
]}

Selkridge, Isaiah ^{[2
]}

Wang, Huan ^{[5
]}

Gomez, Jorge ^{[2
]}

Mascarenhas, John ^{[2
,8
]}

Moe, Aye S. ^{[3
,4
,5
]}

Lau, Chun Yee ^{[3
,4
,5
,13
]}

Taik, Patricia ^{[3
,4
,5
]}

Pandya, Chetanya ^{[3
,4
,14
]}

Sung, Max ^{[2
,8
]}

Kim, Sara ^{[6
]}

Yum, Kendra ^{[6
]}

Sebra, Robert ^{[3
,4
,5
]}

Donovan, Michael ^{[7
,8
]}

Misiukiewicz, Krzysztof ^{[2
,8
]}

Ang, Celina ^{[2
,8
]}

Schadt, Eric E. ^{[3
,4
,5
,8
]}

Posner, Marshall R. ^{[2
,8
]}

Cagan, Ross L. ^{[1
,8
,15
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Cell Dev & Regenerat Biol, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Dept Med Hematol & Med Oncol, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

[4] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA

[5] Sema4, Stamford, CT 06902 USA

[6] Mt Sinai Hosp, Dept Pharm, New York, NY 10029 USA

[7] Icahn Sch Med Mt Sinai, Dept Pathol, New York, NY 10029 USA

[8] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA

[9] Florida State Univ, Dept Biol Sci, B-157, Tallahassee, FL 32306 USA

[10] New York Genome Ctr, Technol Innovat Lab, New York, NY 10013 USA

[11] Univ Virginia, Dept Otolaryngol Head & Neck Surg, Charlottesville, VA 22903 USA

[12] St Georges Univ, Sch Med, St Georges, Grenada

[13] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA

[14] Bluebird Bio, Cambridge, MA 02142 USA

[15] Univ Glasgow, Inst Canc Sci, Glasgow G61 1BD, Lanark, Scotland

来源：

ISCIENCE | 2021年 / 24卷 / 03期

关键词：

biotechnology; cancer systems biology; genetics; molecular physiology;

D O I：

10.1016/j.isci.2021.102212

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Adenoid cystic carcinoma (ACC) is a rare cancer type that originates in the salivary glands. Tumors commonly invade along nerve tracks in the head and neck, making surgery challenging. Follow-up treatments for recurrence or metastasis including chemotherapy and targeted therapies have shown limited efficacy, emphasizing the need for new therapies. Here, we report a Drosophila-based therapeutic approach for a patient with advanced ACC disease. A patient-specific Drosophila transgenic line was developed to model the five major variants associated with the patient's disease. Robotics-based screening identified a three-drug cocktail-vorinostat, pindolol, tofacitinib-that rescued transgene-mediated lethality in the Drosophila patient-specific line. Patient treatment led to a sustained stabilization and a partial metabolic response of 12 months. Subsequent resistance was associated with new genomic amplifications and deletions. Given the lack of options for patients with ACC, our data suggest that this approach may prove useful for identifying novel therapeutic candidates.

引用

页数：25

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