New strategies for targeting drug combinations to overcome mutation-driven drug resistance

Linyan Wang; Haiyun Wang; Dongli Song; Menglin Xu; Michael Liebmen

doi:10.1016/j.semcancer.2016.11.002

New strategies for targeting drug combinations to overcome mutation-driven drug resistance

Semin Cancer Biol. 2017 Feb:42:44-51. doi: 10.1016/j.semcancer.2016.11.002. Epub 2016 Nov 10.

Authors

Linyan Wang¹, Haiyun Wang², Dongli Song³, Menglin Xu³, Michael Liebmen⁴

Affiliations

¹ Zhongshan Hospital Institute of Clinical Science, Fudan University, Shanghai Institute of Clinical Bioinformatics, Biomedical Research Center, Shanghai, China. Electronic address: alick333@126.com.
² School of Life Science and Technology, Tongji University, Shanghai, China.
³ Zhongshan Hospital Institute of Clinical Science, Fudan University, Shanghai Institute of Clinical Bioinformatics, Biomedical Research Center, Shanghai, China.
⁴ Zhongshan Hospital Institute of Clinical Science, Fudan University, Shanghai Institute of Clinical Bioinformatics, Biomedical Research Center, Shanghai, China. Electronic address: m.liebman@strategicmedicine.com.

PMID: 27840276
DOI: 10.1016/j.semcancer.2016.11.002

Abstract

Targeted therapies are suggested as an effective alternative for patients with cancer that harbor mutations, but treatment outcomes are frequently limited by primary or acquired drug resistance. The present review describes potential mechanisms of primary or acquired drug resistances to provide a resource for considering how to be overcome. We focus on strategies of targeted drug combinations to minimize the development of drug resistance within the context how resistance develops. Strategies benefit from the combined use of "omics" technologies, i.e., high-throughput functional genomics data, pharmacogenomics, or genome-wide CRISPR-Cas9 screening, to analyze and design targeted drug combinations for mutation-driven drug resistance. We also introduce new insights towards pathway-centric combined therapies as an alternative to overcome the heterogeneity and benefit patient prognoses.

Keywords: CRISPR-Cas9 screening; Drug resistance; Lung cancer; Pathway-centric therapy; Pharmacogenomics profile; Precision medicine.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols*
Drug Resistance, Neoplasm / genetics*
Genomics
Humans
Molecular Targeted Therapy*
Mutation
Neoplasms / drug therapy*
Neoplasms / genetics
Neoplasms / pathology