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Lung Cancer Heterogeneity and New Strategies for Drug Therapy
Annual Review of Pharmacology and Toxicology ( IF 12.5 ) Pub Date : 2018-01-08 00:00:00 , DOI: 10.1146/annurev-pharmtox-010716-104523
Diane C. Wang, 1 , William Wang, 1 , Bijun Zhu, 1 , Xiangdong Wang 1
Affiliation  

Lung cancer heterogeneity plays an important role in the development of drug resistance. Comprehensive molecular characterizations of lung cancer can describe hereditary and somatic gene changes, mutation, and heterogeneity. We discuss heterogeneity specificity, characterization, and roles of PIK3CD, TP53, and KRAS, as well as target-driven therapies and strategies applied in clinical trials based on a proposed precise self-validation system. The system is a specifically selected strategy of treatment for patients with cancer gene mutations and heterogeneity based on gene sequencing, following validation of the strategies in the patient's own cancer cells or in patient-derived xenografts using their own cancer cells isolated during surgery or biopsies. These results will be more precise if the drugs used in the strategies are selected through protein structure–guided compound screening or a DNA-encoded chemical library before validation in the patient's own cancer cells. Thus, a deeper understanding of heterogeneity mechanisms and improved validation of the therapeutic strategy will result in more precise treatments for patients.

中文翻译:


肺癌的异质性和药物治疗的新策略

肺癌的异质性在耐药性的发展中起着重要作用。肺癌的全面分子特征可以描述遗传和体细胞基因的变化,突变和异质性。我们讨论了PIK3CD,TP53和KRAS的异质性特异性,特征和作用,以及基于拟议的精确自我验证系统的临床试验中目标驱动的疗法和策略。该系统是根据基因测序对具有癌症基因突变和异质性的患者进行特别选择的治疗策略,在对患者自身癌细胞或患者自体异种移植物中使用在手术或活检过程中分离的癌细胞进行的策略验证之后,该策略得以确认。如果在患者自己的癌细胞中进行验证之前,通过蛋白质结构指导的化合物筛选或DNA编码的化学文库选择了该策略中使用的药物,则这些结果将更加精确。因此,对异质性机制的更深入了解和治疗策略的改进验证将为患者带来更精确的治疗方法。

更新日期:2018-01-08
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