Triple Targeting of Breast Tumors Driven by Hormonal Receptors and HER2.

ABSTRACT: Breast cancers that express hormonal receptors (HR) and HER2 display resistance to targeted therapy. Tumor-promotional signaling from the HER2 and estrogen receptor (ER) pathways converges at the cyclin D1 and cyclin-dependent kinases (CDK) 4 and 6 complex, which drives cell-cycle progression and development of therapeutic resistance. Therefore, we hypothesized that co-targeting of ER, HER2, and CDK4/6 may result in improved tumoricidal activity and suppress drug-resistant subclones that arise on therapy. We tested the activity of the triple targeted combination therapy with tucatinib (HER2 small-molecule inhibitor), palbociclib (CKD4/6 inhibitor), and fulvestrant (selective ER degrader) in HR⁺/HER2⁺ human breast tumor cell lines and xenograft models. In addition, we

SUBMITTER: Shagisultanova E 

PROVIDER: S-EPMC8742793 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature