INVESTIGADORES
GIULIANELLI Sebastian Jesus
congresos y reuniones científicas
Título:
Combination of Palbociclib with antiprogestins in experimental breast cancer models with different progesterone receptor isoform ratios
Autor/es:
PATACCINI, GABRIELA; SEQUEIRA, GONZALO; VANZULLI, SILVIA; LANARI, CLAUDIA; GIULIANELLI, SEBASTIÁN
Lugar:
Newry
Reunión:
Conferencia; Gordon Research Conference: Hormone-Dependent Cancers; 2019
Institución organizadora:
Gordon Research Conference
Resumen:
Luminal breast cancers represent more than 70% of all breast cancer patients and they are susceptible to an endocrine therapy. Palbociclib (PALBO), an oral CDK 4/6 inhibitor, is currently used in combination with endocrine therapy to treat advanced hormone receptor-positive, HER2-negative breast cancer. While this treatment doubles time to progression compared to endocrine therapy alone, about 25-35% of patients do not respond, and almost all patients eventually acquire resistance. Therefore, alternative therapies are required to reduce breast cancer mortality. We have recently reported that breast cancer patients with tumors expressing higher levels of isoform A of the progesterone receptor (PRA) than isoform B (PRB) may benefit from an antiprogestin treatment. The aim of this study was to evaluate the effect of cell cycle inhibitors in combination with antiprogestins in luminal mouse and human experimental breast cancer models. We first tested the effects of the antiprogestin mifepristone (MFP; 10 nM) and/or PALBO (100 nM) on cell proliferation using the T47D breast cancer cells and the T47D-YA and T47D-YB variants expressing only PRA or PRB respectively, provided by the Horwitz Laboratory. Cells were incubated in the presence of 5% steroid stripped fetal calf serum and FGF2 (50 ng/ml) in order to have a basal high proliferative state. T47D and T47D-YA FGF2-treated cells were inhibited by MFP, or PALBO (p