Journal
EXPERIMENTAL BIOLOGY AND MEDICINE
Volume 243, Issue 17-18, Pages 1245-1255Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1535370218820287
Keywords
Liver metastasis; metastatic models; tumor microenvironment; hepatic niche; microphysiological
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Funding
- NIH [UH3TR000496]
- VA Merit Award
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Cancer mortality ensues from metastatic growths. Cancers use two strategies to allow for this unrelenting expansion. The first way is that early metastases are often cryptic or dormant, being invisible to both innate suppressive actions and undetected clinically. Second, both the micrometastases and later clinically lethal growths are resistant to therapies, whether standard chemotherapies, targeted biologics, or even immunotherapies. These two modes of resistance necessitate new approaches to treatments if we are to eliminate mortality from solid tumors. However, to develop such therapeutic strategies, we first need to better understand the cellular behaviors and molecular events that enable the resistances. Herein, we present a comprehensive model of changing methods of avoidance and resistance that occur during tumor progression, and doubly confound treatment by mixing survival strategies throughout the continuum creating moving targets. Melanoma is presented as the model cancer, as it is being targeted by all three types of agents for disseminated disease, with breast and prostate cancer as two other key carcinomas.
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