Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Bangi E

PROVIDER: S-EPMC7940980 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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

Bangi Erdem E Smibert Peter P Uzilov Andrew V AV Teague Alexander G AG Gopinath Sindhura S Antipin Yevgeniy Y Chen Rong R Hecht Chana C Gruszczynski Nelson N Yon Wesley J WJ Malyshev Denis D Laspina Denise D Selkridge Isaiah I Wang Huan H Gomez Jorge J Mascarenhas John J Moe Aye S AS Lau Chun Yee CY Taik Patricia P Pandya Chetanya C Sung Max M Kim Sara S Yum Kendra K Sebra Robert R Donovan Michael M Misiukiewicz Krzysztof K Ang Celina C Schadt Eric E EE Posner Marshall R MR Cagan Ross L RL

iScience 20210220 3

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 dev ...[more]

PMID: 33733072

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Project description:PurposeAdenoid cystic carcinoma of the breast (ACCB) is a rare malignancy with a favorable prognosis. Little information exists regarding the impact of postoperative radiation therapy (RT) on survival outcome in patients with ACCB. This study aimed to evaluate the clinical significance of postoperative RT in ACCB.MethodsData of patients with ACCB were extracted from the Surveillance, Epidemiology, and End Results database (2000-2019). Univariate and multivariable Cox regression analyses were performed to identify prognostic factors. In addition, a nomogram model was constructed and internally validated for discrimination and calibration. The value of postoperative RT was respectively accessed in each risk subgroup according to nomogram-deduced individualized score.ResultsA total of 689 eligible patients were included in the analysis. Partial mastectomy was associated with an increased risk of death compared with partial mastectomy plus postoperative RT (P = 0.020), but total mastectomy with or without postoperative RT was comparable (P = 0.624). Then, in-depth analysis was performed for patients receiving breast-conserving therapy (n = 485, the training set vs. the testing set = 340 vs. 145). Age at diagnosis, histological grade, and T stage were identified as prognostic factors for overall survival (OS) (All P < 0.05). A nomogram was constructed to provide predictive accuracy toward individual OS rates of ACCB and to divide patients into different risk subgroups. Notably, compared with non-RT, postoperative RT significantly improved OS in the high-risk subgroup (P = 0.006 for the training set, and P = 0.013 for the overall population) but not in the low-risk subgroup (P = 0.807 for the training set, and P = 0.293 for the overall population), suggesting that these patients may be able to exempt from postoperative RT.ConclusionA robust and effective nomogram was developed to predict prognosis and assist in treatment decisions in patients with ACCB undergoing partial mastectomy.

Dataset Information

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

Publications

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

Similar Datasets

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