scholarly journals Defects in mismatch repair: the Achilles heel of estrogen receptor positive breast cancer with intrinsic endocrine therapy resistance?

Oncoscience ◽  
2017 ◽  
Vol 4 (7-8) ◽  
pp. 77-78 ◽  
Author(s):  
Svasti Haricharan ◽  
Matthew J. Ellis
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Mismatch Repair ◽  
Endocrine Therapy ◽  
Therapy Resistance ◽  
Endocrine Therapy Resistance ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

scholarly journals Estrogen-regulated feedback loop limits the efficacy of estrogen receptor–targeted breast cancer therapy

2018 ◽  
Vol 115 (31) ◽  
pp. 7869-7878 ◽  
Author(s):  
Tengfei Xiao ◽  
Wei Li ◽  
Xiaoqing Wang ◽  
Han Xu ◽  
Jixin Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Therapy Resistance ◽  
Negative Feedback Loop ◽  
Endocrine Therapy Resistance ◽  
Estrogen Receptor Positive ◽  
Underlying Mechanisms

Endocrine therapy resistance invariably develops in advanced estrogen receptor-positive (ER+) breast cancer, but the underlying mechanisms are largely unknown. We have identified C-terminal SRC kinase (CSK) as a critical node in a previously unappreciated negative feedback loop that limits the efficacy of current ER-targeted therapies. Estrogen directly drives CSK expression in ER+ breast cancer. At low CSK levels, as is the case in patients with ER+ breast cancer resistant to endocrine therapy and with the poorest outcomes, the p21 protein-activated kinase 2 (PAK2) becomes activated and drives estrogen-independent growth. PAK2 overexpression is also associated with endocrine therapy resistance and worse clinical outcome, and the combination of a PAK2 inhibitor with an ER antagonist synergistically suppressed breast tumor growth. Clinical approaches to endocrine therapy-resistant breast cancer must overcome the loss of this estrogen-induced negative feedback loop that normally constrains the growth of ER+ tumors.

Endocrine therapy resistance in estrogen receptor (ER)-positive breast cancer

2016 ◽  
Vol 21 (7) ◽  
pp. 1181-1188 ◽  
Author(s):  
Tommaso De Marchi ◽  
John A. Foekens ◽  
Arzu Umar ◽  
John W.M. Martens
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Therapy Resistance ◽  
Endocrine Therapy Resistance ◽  
Er Positive ◽  
Positive Breast Cancer
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