New in vitro system to predict chemotherapeutic efficacy of drug combinations in fresh tumor samples

PeerJ

article

Frank Christian Kischkel¹  Julia Eich¹  Carina I. Meyer¹  Paula Weidemüller¹  Jens Krapfl¹  Rauaa Yassin-Kelepir¹  Laura Job¹  Marius Fraefel¹  Ioana Braicu²  Annette Kopp-Schneider³  Jalid Sehouli²  Rudy Leon De Wilde⁴ 

[1] TherapySelect;Gynecology Department, Charité Berlin, Virchow Campus Berlin;Division of Biostatistics, German Cancer Research Center;University Hospital for Gynecology, Carl von Ossietzky University Oldenburg

关键词: Chemotherapy-resistance-test;    Drug combination;    Ovarian carcinoma;    Drug combination testing;    Additive effect;    Drug sensitivity testing;    Individualized cancer therapy;   

DOI  :  10.7717/peerj.3030

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundTo find the best individual chemotherapy for cancer patients, the efficacy of different chemotherapeutic drugs can be predicted by pretesting tumor samples in vitro via the chemotherapy-resistance (CTR)-Test®. Although drug combinations are widely used among cancer therapy, so far only single drugs are tested by this and other tests. However, several first line chemotherapies are combining two or more chemotherapeutics, leading to the necessity of drug combination testing methods.MethodsWe established a system to measure and predict the efficacy of chemotherapeutic drug combinations with the help of the Loewe additivity concept in combination with the CTR-test. A combination is measured by using half of the monotherapy’s concentration of both drugs simultaneously. With this method, the efficacy of a combination can also be calculated based on single drug measurements.ResultsThe established system was tested on a data set of ovarian carcinoma samples using the combination carboplatin and paclitaxel and confirmed by using other tumor species and chemotherapeutics. Comparing the measured and the calculated values of the combination testings revealed a high correlation. Additionally, in 70% of the cases the measured and the calculated values lead to the same chemotherapeutic resistance category of the tumor.ConclusionOur data suggest that the best drug combination consists of the most efficient single drugs and the worst drug combination of the least efficient single drugs. Our results showed that single measurements are sufficient to predict combinations in specific cases but there are exceptions in which it is necessary to measure combinations, which is possible with the presented system.

【 授权许可】

CC BY