期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 21, 期 19, 页码 -出版社
MDPI
DOI: 10.3390/ijms21197304
关键词
metastasis; disseminated tumor cells; e-cadherin; therapy resistance; dormancy; metastatic microenvironment; immune checkpoint blockade; epigenetics; metabolic plasticity
资金
- VA Merit Award program
- National Institutes of Health [UH3TR000496, GM69668, GM63569]
- Department of Defense [W81XWH-19-1-0494]
Metastatic spread represents the leading cause of disease-related mortality among cancer patients. Many cancer patients suffer from metastatic relapse years or even decades after radical surgery for the primary tumor. This clinical phenomenon is explained by the early dissemination of cancer cells followed by a long period of dormancy. Although dormancy could be viewed as a window of opportunity for therapeutic interventions, dormant disseminated cancer cells and micrometastases, as well as emergent outgrowing macrometastases, exhibit a generalized, innate resistance to chemotherapy and even immunotherapy. This therapeutic pan-resistance, on top of other adaptive responses to targeted agents such as acquired mutations and lineage plasticity, underpins the current difficulties in eradicating cancer. In the present review, we attempt to provide a framework to understand the underlying biology of this major issue.
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