期刊
BIOMEDICINES
卷 9, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines9111591
关键词
cancer; targeted therapies; resistance mechanisms; receptor tyrosine kinases; single kinase inhibitors; multikinase inhibitors; clinical trial inhibitors; combination drug therapies
资金
- American Society of Hematology
- Robert Wood Johnson Foundation
- Edward P. Evans MDS Foundation
- Doris Duke Charitable Foundation
- NIH/NCI [1K08CA230319-01]
Development of targeted therapies has provided nonchemotherapeutic options for patients, with small molecule kinase inhibitors being a key focus. However, resistance to these therapies may develop, necessitating multiple lines of treatment. Combinations of therapies targeting complimentary pathways may be more effective in overcoming drug resistance.
Development of targeted therapies in recent years revealed several nonchemotherapeutic options for patients. Chief among targeted therapies is small molecule kinase inhibitors targeting key oncogenic signaling proteins. Through competitive and noncompetitive inhibition of these kinases, and therefore the pathways they activate, cancers can be slowed or completely eradicated, leading to partial or complete remissions for many cancer types. Unfortunately, for many patients, resistance to targeted therapies, such as kinase inhibitors, ultimately develops and can necessitate multiple lines of treatment. Drug resistance can either be de novo or acquired after months or years of drug exposure. Since resistance can be due to several unique mechanisms, there is no one-sizefits-all solution to this problem. However, combinations that target complimentary pathways or potential escape mechanisms appear to be more effective than sequential therapy. Combinations of single kinase inhibitors or alternately multikinase inhibitor drugs could be used to achieve this goal. Understanding how to efficiently target cancer cells and overcome resistance to prior lines of therapy became imperative to the success of cancer treatment. Due to the complexity of cancer, effective treatment options in the future will likely require mixing and matching these approaches in different cancer types and different disease stages.
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