TY - JOUR
T1 - Experimental models of endocrine responsive breast cancer
T2 - Strengths, limitations, and use
AU - Clarke, Robert
AU - Jones, Brandon C.
AU - Sevigny, Catherine M.
AU - Hilakivi-Clarke, Leena A.
AU - Sengupta, Surojeet
N1 - Publisher Copyright:
© The Author(s) 2021.
PY - 2021
Y1 - 2021
N2 - Breast cancers characterized by expression of estrogen receptor-alpha (ER; ESR1) represent approximately 70% of all new cases and comprise the largest molecular subtype of this disease. Despite this high prevalence, the number of adequate experimental models of ER+ breast cancer is relatively limited. Nonetheless, these models have proved very useful in advancing understanding of how cells respond to and resist endocrine therapies, and how the ER acts as a transcription factor to regulate cell fate signaling. We discuss the primary experimental models of ER+ breast cancer including 2D and 3D cultures of established cell lines, cell line- and patient-derived xenografts, and chemically induced rodent models, with a consideration of their respective general strengths and limitations. What can and cannot be learned easily from these models is also discussed, and some observations on how these models may be used more effectively are provided. Overall, despite their limitations, the panel of models currently available has enabled major advances in the field, and these models remain central to the ability to study mechanisms of therapy action and resistance and for hypothesis testing that would otherwise be intractable or unethical in human subjects.
AB - Breast cancers characterized by expression of estrogen receptor-alpha (ER; ESR1) represent approximately 70% of all new cases and comprise the largest molecular subtype of this disease. Despite this high prevalence, the number of adequate experimental models of ER+ breast cancer is relatively limited. Nonetheless, these models have proved very useful in advancing understanding of how cells respond to and resist endocrine therapies, and how the ER acts as a transcription factor to regulate cell fate signaling. We discuss the primary experimental models of ER+ breast cancer including 2D and 3D cultures of established cell lines, cell line- and patient-derived xenografts, and chemically induced rodent models, with a consideration of their respective general strengths and limitations. What can and cannot be learned easily from these models is also discussed, and some observations on how these models may be used more effectively are provided. Overall, despite their limitations, the panel of models currently available has enabled major advances in the field, and these models remain central to the ability to study mechanisms of therapy action and resistance and for hypothesis testing that would otherwise be intractable or unethical in human subjects.
KW - Breast cancer
KW - Experimental models
KW - PDX
KW - Study design
KW - Xenografts
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U2 - 10.20517/cdr.2021.33
DO - 10.20517/cdr.2021.33
M3 - Review article
C2 - 34532657
AN - SCOPUS:85118324444
SN - 2578-532X
VL - 4
SP - 762
EP - 783
JO - Cancer Drug Resistance
JF - Cancer Drug Resistance
IS - 4
ER -