Cyclacel Pharmaceuticals highlights study from independent investigators
Cyclacel Pharmaceuticals highlighted a paper from independent investigators published in the most recent edition of the Journal of Clinical Oncology. The study findings identify overexpression of cyclin E1 as a mechanism by which breast cancer escapes the effects of palbociclib CDK4/6 inhibitor plus fulvestrant treatment. Inhibition of the CDK2/cyclin E complex, the target of Cyclacel's CYC065 clinical stage candidate, is proposed as a potential therapeutic approach to prevent early progression on CDK4/6 inhibitors. In the PALOMA-3 trial, patients with endocrine therapy-pretreated, metastatic breast cancer were randomized to receive palbociclib with fulvestrant or placebo with fulvestrant. Out of 521 patients treated 302 had tumor tissue analyzed. Palbociclib efficacy was approximately halved in patients with high compared to low cyclin E1 expression in their tumors. In contrast to cyclin E1 expression, the analysis showed that expression of cyclin D1, the molecular partner of CDKs 4 and 6 which are the targets of palbociclib, or PI3 kinase, or PIK3CA, mutations were not predictive of efficacy for palbociclib plus hormone therapy. The findings were further validated through a gene expression analysis of the POP trial in 61 patients with untreated early-stage breast cancer receiving either palbociclib until the day before surgery or no treatment. High cyclin E expression was associated with lower absolute antiproliferative response to palbociclib. Correlative analysis of PALOMA-3 data has identified cyclin E1 as the first potential biomarker that is predictive of the efficacy of palbociclib.