Development of combinatorial drug against EGFR mutation in non-small cell lung cancer treatment

碩士 === 國立交通大學 === 分子醫學與生物工程研究所 === 102 === Oncologists are facing formidable challenges in overcoming cancers with either innate or acquired resistance to cancer therapies, especially for the cancers with EGFR mutation and activation. Therefore, the development of new drugs against drug resistance o...

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Bibliographic Details
Main Authors: Huang, Yi-Ning, 黃薏寧
Other Authors: Ho, Shinn-Ying
Format: Others
Language:zh-TW
Published: 2014
Online Access:http://ndltd.ncl.edu.tw/handle/46220197275366201244
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Summary:碩士 === 國立交通大學 === 分子醫學與生物工程研究所 === 102 === Oncologists are facing formidable challenges in overcoming cancers with either innate or acquired resistance to cancer therapies, especially for the cancers with EGFR mutation and activation. Therefore, the development of new drugs against drug resistance of the EGFR-mutation cancer is one of the major cancer researches. There is a general agreement that multiple-target molecules might be more effective than single-target agents. Chinese herbal medicines are becoming important resources for designing multi-target bioactive molecules. Combination therapy is one of the well-studied multiple-target approaches, gradually used to treat various types of diseases, including cancers. Hence, this work investigates nine Chinese herbal medicines (Herba Hedyotidis, Radix Platycodonis, Herba Houttuyniae, Herba Scutellariae barbatae, Rhizoma Pinelliae preparata, Radix Scutriae, Rellaadix Salviae miltiorrhizae, Cortex Magnoliae officinalis, and Bulbus Fritillariae thunbergii). These herbs are frequently used in the herbal medication to treat non-small cell lung cancer (NSCLC) patients. Afterwards, these nine Chinese herbal medicines are combined and then treated in normal lung cell line (BEAS-2B), EGFR wild type cell line (NCI-H292), EFGR mutation (HCC827) and double mutation cell lines (NCI-H1975). The drug dose and combination are determined based on an orthogonal experimental design method. The objective of the combined Chinese herbal medicine is to minimize the number of cancel cells survived and to maximize the number of normal cells survived. Consequently, the mechanism of the combination drug via cell apoptosis induction is further validated. This work purposes a combination drug with optimized dosage that is potentially effective to copes with the drug resistance to the EGFR-mutation therapy for NSCLC patients.