Rock Creek Pharmaceuticals Inc. (fka RCPIQ)

[Buddhahead]

The NFkB pathway and endocrine-resistant breast cancer Conference Paper in Endochronology Journal, Y Zhou, S Eppenberger-Castori1
, U Eppenberger1 and C C Benz, Buck Institute for Age Research, Novato, California 94945, USA, 1 Stiftung Tumorbank Basel, Lo¨rracherstrasse 50, CH-4125 Riehen, Switzerland, 2005

Abstract:
"Endocrine therapy with an estrogen receptor (ER)-targeted antiestrogen, such as tamoxifen, or estrogen ablation by aromatese inhibitors is clinically indicated for the management of all forms of ER-positive breast cancer. However 30-50% of ER-positive breast cancer cases fail to benefit clinically from endocrine therapy alone, and recent molecular evidence suggests that 'crosstalk' pathways originating from activated receptor tyosine kinases and/or other roliferative and survival signals may be contributing to this endocrine resistance. Molecular identification and validation of candidate ER crosstalking pathways will likely lead to clinically important prognostic markers and targets for the application of novel therapeutics in combination with standard endocrine agents. This review focuses on a critical survival and proliferation pathway involving activation of nuclear factor-kB (NF-kB), a family of ubiquitously expressed transcription factors that for nearly two decades have been known to be critical regulators of mammalian immune and inflammatory responses, and more recently have been associated with chemotherapy resistance. With the demonstration that activation of NF-kB is absolutely required for normal mammary gland development, NF-kB invovement in human breast cancers was initially explored and linked in the development of hormone-independent(ER-negative) breast cancer. Newer clinical evidence now implicates NF-kB activation, particularly DNA-binding by the p50 subunit of NF-kB, as a potential prognostic marker capable of identifying high-risk subset of ER-positive, primary breast cancers destined for early relapse despite adjuvant endocrine therapy with tamoxifen. Furthermore, initial preclinical studies suggest that treatment strategies designed to prevent or interrupt activation of NF-kB in cell-line models of these more aggressive, ER-positive breast cancers can restore their sensitivity to such standard endocrine agents as tamoxifen.

Article at:
http://erc.endocrinology-journals.org/content/12/Supplement_1/S37.full.pdf