PALBOCICLIB RESPONSIVENESS OF THE MPA-IN- DUCED MURINE BREAST CANCER MODEL WITH DIF- FERENT SENSITIVITY TO ENDOCRINE TREATMENTS

PATACCINI, GABRIELA; ELIA, ANDRES; ABBA, MARTIN; LANARI, CLAUDIA; GIULIANELLI, SEBASTIÁN

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

SAIC SAB AAFE AACYTAL

Luminal breast carcinomas represent more than 70% of all breast cancer (BC) patients. Palbociclib (PALBO), an oral CDK 4/6 inhibitor, is currently used in combination with endocrine therapy to treat advanced hormone receptor-positive, HER2-negative BC. However, about 25-35% of patients do not respond, and almost all patients, eventually, become resistant to this treatment. We have demonstrated that two tumor families from the MPA-induced BC murine model have a differential response to PALBO, regardless their response to an antiprogestin treatment (mifepristone, MFP), being the 59 family sensitive and the C4 family resistant to PALBO. The aim of the study was to evaluate the basal pRB expression, its regulation upon PALBO treatment and the transcriptome difference in both families that may shed light to understand their differential response to PALBO.RB phosphorylation levels were evaluated by IHC in 59-2-HI, 59-HI, C4-HI and C4-2-HI tumors after approximately 15 days of vehicle or PALBO treatment. RNA-Seq studies were carried out using RNAfrom untreated tumors. The differential expression and enrichment analysis were conducted with R/Bioconducter packages. As expected, pRB expression in the 59 tumors decreased after PALBO treatment (p