Endocrine therapy is the most effective treatment option for estrogen-receptor (ER) positive breast cancer, but its efficacy is limited by both intrinsic and acquired endocrine resistance. Roughly a quarter of patients with primary tumors and nearly all patients with metastases will eventually develop endocrine resistance. While the mechanism of endocrine resistance remains poorly understood, emerging evidence suggests that mutations or fusions of the ESR1 gene are important driving mechanisms.
Description
Recent research on one of the most common recurrent ESR1 fusions, ESR1-CCDC170, show that different fusions endow different levels of reduced endocrine sensitivity in vivo, as well as a novel mechanism by which it binds to receptors HER2/HER3/SRC and activates SRC/PI3K/AKT signaling. Silencing ESR1-CCDC170 downregulates HER2/HER3 and improves endocrine sensitivity. Most importantly, these developments indicate that breast cancer cells expressing ectopic or endogenous forms of this ESR1 fusion are highly sensitivity to concomitant treatment with tamoxifen and dasatinib. A detection assay for ESR1-CCDC170 may be used in the clinic to determine which patients are best suited for SRC-targeted therapy, preventing patients from undergoing ineffective treatments and concentrating resources on those who would most benefit.
Applications
· Stratifying breast cancer patients by suitability for SRC-targeted therapy
Advantages
· There are no other assays that can match patients with this fusion gene to SRC-targeted therapy
Invention Readiness
In vitro data
IP Status
https://patents.google.com/patent/US20230175069A1
