Activation of the Phosphatidylinositol 3-kinase (PI3K) pathway is common in Estrogen receptor (ER)-positive breast cancer (BC) and it has been associated with resistance to endocrine therapies (ET). The crosstalk between the Cyclin-dependent kinase 4/6 (CDK4/6) and PI3K pathways represents a strong rationale for co-targeting both axes to inhibit tumor growth. Moreover, combined treatment with PI3K and CDK4/6 inhibitors has been shown to overcome CDK4/6 inhibitor resistance in BC cells. We investigated the triple combination of ER, CDK4/6, and PI3K pathway inhibitors in
We generated 25
Our results demonstrated that combination of F, P and T had a synergistic effect on the inhibition of spheroids proliferation in ≈30% of the examined samples compared to single drug treatments. Two subgroups of samples with different behavior were identified: one group showed no effect after single or triple treatment with only ≈15% reduction in cell viability (probably resistant) while the other group exhibited greater sensitivity to treatments (e.g. lobular histotype). Ongoing NGS analysis including a full panel of cancer-related genes, such as genes involved in CDK and PI3K pathways resistance. We will analyze concordance between surgical samples and
The results showed an encouraging activity of the triple combination of ER, CDK4/6, and PI3K pathway inhibitors in ex vivo models of ER-positive BC. The different effect of the treatments could suggest a correlation between mutation setting and individual response.
University of Campania.
Pfizer.
All authors have declared no conflicts of interest.