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Cytoplasmic Cyclin E Mediates Resistance To Aromatase Inhibitors In Breast Cancer, Iman Doostan
Cytoplasmic Cyclin E Mediates Resistance To Aromatase Inhibitors In Breast Cancer, Iman Doostan
Dissertations & Theses (Open Access)
Almost seventy percent of patients with breast cancer have tumors that express hormone receptors and need hormonal therapy. Aromatase inhibitors (AIs) block estrogen biosynthesis and are considered as the first line hormonal therapy for ER+ post-menopausal patients. However, resistance to these drugs remains a major challenge in clinic and the biology of such resistance is not completely understood. Cyclin E is deregulated in breast cancer through generation of low molecular weight isoforms that renders patients to a poor survival. Herein, we show that HR+ patients with LMW-E expressing tumors show diminished early response to neo-adjuvant AIs as well as …
Targeting Autophagy To Improve Efficacy Of Cdk4/6 Inhibition In Breast Cancer, Smruthi Vijayaraghavan
Targeting Autophagy To Improve Efficacy Of Cdk4/6 Inhibition In Breast Cancer, Smruthi Vijayaraghavan
Dissertations & Theses (Open Access)
Deregulation of the cell cycle machinery is a hallmark of cancer, leading to aberrant proliferation and tumorigenesis. The crucial role of the CDK4/6-Cyclin D pathway has led to the development and FDA approval (palbociclib, ribociclib) of CDK4/6 inhibitors for the treatment of advanced estrogen receptor positive breast cancer. However, three major clinical challenges remain: i) adverse events leading to discontinuation of therapy and ii) lack of reliable biomarkers to identify responsive patients and iii) acquired resistance to CDK4/6 inhibitors. Previous in vitro studies have shown that palbociclib mediated CDK4/6 inhibition induces G1 arrest and senescence in ER+ breast cancer cells, …