Identification of Genetic Mutations in Cancer: Challenge and Opportunity in the New Era of Targeted Therapy

Frontiers in Oncology

Liping Qu¹  Jing Li²  Qinglian Wen³  Jing Jin³  Jingbo Wu³  Zhangang Xiao⁴  Tao Yi⁵  Mingxing Li⁶  Yueshui Zhao⁶  Jianhua Yin⁶  Chi Hin Cho⁶  Xu Wu⁶  Qijie Zhao⁶  Jing Shen⁶ 

[1] College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China;Department of Oncology and Hematology, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, China;Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China;Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China;School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China;South Sichuan Institute of Translational Medicine, Luzhou, China;

关键词: targeted therapy;    cyclin-dependent kinases 4/6;    somatic mutation;    resistance;    EGFR;    PD-1/PD-L1;   

DOI  :  10.3389/fonc.2019.00263

来源: DOAJ

【 摘 要 】

The introduction of targeted therapy is the biggest success in the treatment of cancer in the past few decades. However, heterogeneous cancer is characterized by diverse molecular alterations as well as multiple clinical profiles. Specific genetic mutations in cancer therapy targets may increase drug sensitivity, or more frequently result in therapeutic resistance. In the past 3 years, several novel targeted therapies have been approved for cancer treatment, including drugs with new targets (i.e., anti-PD1/PDL1 therapies and CDK4/6 inhibitors), mutation targeting drugs (i.e., the EGFR T790M targeting osimertinib), drugs with multiple targets (i.e., the EGFR/HER2 dual inhibitor neratinib) and drug combinations (i.e., encorafenib/binimetinib and dabrafenib/trametinib). In this perspective, we focus on the most up-to-date knowledge of targeted therapy and describe how genetic mutations influence the sensitivity of targeted therapy, highlighting the challenges faced within this era of precision medicine. Moreover, the strategies that deal with mutation-driven resistance are further discussed. Advances in these areas would allow for more targeted and effective therapeutic options for cancer patients.

【 授权许可】

Unknown