A Role for Estrogen Receptor Phosphorylation in the Resistance to Tamoxifen

About two thirds of all human breast cancer cases are estrogen receptor positive. The drug of first choice for these patients is tamoxifen. However, about half of the recurrences after removal of the primary tumor are or become resistant to this drug. While many mechanisms have been identified for tamoxifen resistance in the lab, at present only a few have been translated to the clinic. This paper highlights the role in tamoxifen resistance of phosphorylation by different kinases on different sites of the estrogen receptor. We will discuss the molecular pathways and kinases that are involved in phosphorylation of ERα and how these affect tamoxifen resistance. Finally, we will elaborate on the clinical translation of these observations and the possibility to predict tamoxifen responses in patient tumor samples before treatment onset. The findings made originally on the bench may translate into a better and personalized treatment of breast cancer patients using an old and safe anticancer drug: tamoxifen

Protein Kinase A-induced tamoxifen resistance is mediated by anchoring protein AKAP13

Univariate analysis for different AKAP13 probes. Table S2. Univariate analysis. Table S3. Multivariate analysis. (PDF 64 kb

Agile Entwicklung physischer Produkte 2023: Eine Studie zum aktuellen Stand in der industriellen Praxis

In der Entwicklung von mechatronischen Produkten nimmt die agile Entwicklung bereits seit einigen Jahren eine zunehmend wichtigere Rolle ein. Im Rahmen dieser Studienserie wird seit 2018 das Fortschreiten der Agilität in der DACH-Region untersucht. In der vorliegenden Ausgabe des Jahres 2023 liegt der Fokus dem Verständnis und der Anwendung agiler Arbeitsweisen, den Herausforderungen in deren Skalierung und der Bedeutung von Prototyping im genannten Kontext. Die Ergebnisse dieser Studie beruhen, wie auch in den vorangegangenen Jahren, auf den Aussagen von Praktikern aus einem breiten Spektrum an Industrieunternehmen, die an einer Online-Umfrage teilgenommen haben. Die Studie beschreibt sowohl quantitative als auch qualitative Ergebnisse aus der industriellen Praxis

Cyclin A is a prognostic indicator in early stage breast cancer with and without tamoxifen treatment

Overexpression of G1-S regulators cyclin D1 or cyclin A is frequently observed in breast cancer and is also to result in ligand-independent activation of oestrogen receptor in vitro. This might therefore, provide a mechanism for failure of tamoxifen treatment. We examined by immunohistochemical staining the effect of deregulation of these, and other cell cycle regulators on tamoxifen treatment in a group of 394 patients with early stage breast cancer. In univariate analysis, expression of cyclin A, Neu, Ki-67 index, and lack of OR expression were significantly associated with worse prognosis. When adjusted by the clinical model (for lymph node status, age, performance status, T-classification, grade, prior surgery, oestrogen receptor status and tamoxifen use), only overexpression of cyclin A and Neu were significantly associated with worse prognosis with hazard ratios of, respectively, 1.709 (P=0.0195) and 1.884 (P=0.0151). Overexpression of cyclin A was found in 86 out of the 201 OR-positive cases treated with tamoxifen, and was the only independent marker associated with worse prognosis (hazard ratio 2.024, P=0.0462). In conclusion, cyclin A is an independent predictor of recurrence of early stage breast cancer and is as such a marker for response in patients treated with tamoxifen

The End of the Marxist-Legal-Theories in Japan (3)

With current techniques, it remains a challenge to assess coregulator binding of nuclear receptors, for example, the estrogen receptor alpha (ERa). ERα is critical in many breast tumors and is inhibited by antiestrogens such as tamoxifen in cancer therapy. ERα is also modified by acetylation and phosphorylation that affect responses to the antiestrogens as well as interactions with coregulators. Phosphorylation of ERα at Ser305 is one of the mechanisms causing tamoxifen resistance. Detection of resistance in patient samples would greatly facilitate clinical decisions on treatment, in which such patient