Abstract 4766: Establishment of drug sensitivity and resistance testing using focused drug libraries to develop targeted therapies for patients with leukemia
| Autor: | Justin J. Montoya, Robert J. Arceci, David O. Azorsa, Apurvi Patel, Daniel H. Wai |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Drug
Oncology Cancer Research medicine.medical_specialty Chemotherapy business.industry media_common.quotation_subject medicine.medical_treatment Ponatinib Cancer Pharmacology medicine.disease Precision medicine Targeted therapy chemistry.chemical_compound Leukemia Pharmacotherapy chemistry Internal medicine medicine business media_common |
| Zdroj: | Cancer Research. 76:4766-4766 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2016-4766 |
| Popis: | Despite major advancements in pediatric leukemia therapy, toxicities and morbidity from chemotherapy regimens have been detrimental. Advances in genomic research as well as precision medicine have helped identify specific mutations that may be susceptible to targeted therapy in leukemic patients. Overall, the use of targeted drug therapy is rising in the pediatric oncology field. To complement genomic analysis of leukemia patients, our laboratory is working on the development of a drug sensitivity and resistance screening library, that would provide functionally relevant drug response data of the patient's leukemia cells. Development of this assay included the preparation of pre-dosed library plates allowing for rapid initiation of the assay. Cells were treated for 72 hours and cell viability was determined. Preliminary work in our laboratory used a library of 56 anti-cancer and targeted agents, which were tested on 16 AML cell lines and 10 ALL cell lines. Biological replicates were preformed for each cell line and drug response data in the form of IC50s and Area Under the Curve (AUC) were calculated. Hierarchical clustering was performed to determine similar responses between cell lines. Our results identified several cell lines that showed hypersensitivity to specific drugs. Among them, the AML cell line KG-1a showed sensitivity to three FGFR inhibitors including Ponatinib, which was previously reported. Validation of the screening results was done using a 10-concentration drug dose response assay. Further testing will include expansion of our drug library and application to ex vivo patient samples. The results from these studies can lead to the establishment of a drug sensitivity and resistance assay that could provide specifically engineered therapies for each patient. This form of personalized therapy would lead to diminished toxicities from systemic therapies as well as allow increased cure rates. Citation Format: Apurvi Patel, Justin J. Montoya, Daniel H. Wai, Robert J. Arceci, David O. Azorsa. Establishment of drug sensitivity and resistance testing using focused drug libraries to develop targeted therapies for patients with leukemia. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4766. |
| Databáze: | OpenAIRE |
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