Lung Cancer Heterogeneity and New Strategies for Drug Therapy

被引:59
作者
Wang, Diane C. [1 ]
Wang, William [1 ]
Zhu, Bijun [1 ]
Wang, Xiangdong [1 ]
机构
[1] Fudan Univ, Ctr Clin Bioinformat, Shanghai Inst Clin Bioinformat, Zhongshan Hosp,Inst Clin Sci, Shanghai 200032, Peoples R China
来源
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 58 | 2018年 / 58卷
关键词
lung cancer; heterogeneity; therapeutic strategy; gene mutations; target drugs; COMPREHENSIVE MOLECULAR CHARACTERIZATION; TUMOR HETEROGENEITY; GENOMIC INSTABILITY; COLORECTAL-CANCER; TP53; MUTATIONS; CELL; DNA; GROWTH; MECHANISMS; RESISTANCE;
D O I
10.1146/annurev-pharmtox-010716-104523
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:531 / 546
页数:16
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