TY - JOUR
T1 - Identification of Genetic Mutations in Cancer
T2 - Challenge and Opportunity in the New Era of Targeted Therapy
AU - Jin, Jing
AU - Wu, Xu
AU - Yin, Jianhua
AU - Li, Mingxing
AU - Shen, Jing
AU - Li, Jing
AU - Zhao, Yueshui
AU - Zhao, Qijie
AU - Wu, Jingbo
AU - Wen, Qinglian
AU - Cho, Chi Hin
AU - Yi, Tao
AU - Xiao, Zhangang
AU - Qu, Liping
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (Grant nos. 81503093, 81602166, and 81672444) and the Joint Funds of the Southwest Medical University and Luzhou (2016LZXNYD-T01, 2017LZXNYD-Z05, and 2017LZXNYD-J09). The funding from National Natural Science Foundation of China (Grant nos. 81503093) will cover open access fee.
Publisher copyright:
© 2019 Jin, Wu, Yin, Li, Shen, Li, Zhao, Zhao, Wu, Wen, Cho, Yi, Xiao and Qu
PY - 2019/4/16
Y1 - 2019/4/16
N2 - 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.
AB - 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.
KW - Cyclin-dependent kinases 4/6
KW - EGFR
KW - PD-1/PD-L1
KW - Resistance
KW - Somatic mutation
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85066734521&partnerID=8YFLogxK
U2 - 10.3389/fonc.2019.00263
DO - 10.3389/fonc.2019.00263
M3 - Review article
AN - SCOPUS:85066734521
SN - 2234-943X
VL - 9
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 263
ER -