While many advances have been made in breast cancer treatments, the management of more aggressive and metastatic tumors remains a central clinical challenge. It is unclear why some patients with clinically localized breast cancer are prone to develop metastatic disease and it is hard to determine who will require more aggressive treatments and intensive follow-ups. To make the matter worse, once distant metastasis is developed, the disease becomes incurable, and the management options are limited to palliative treatments.
Description
Researchers at University of Pittsburgh have discovered a non-traditional molecular event underlying molecular pathobiology of more aggressive and metastatic breast cancer. In this study, a large-scale analysis of breast cancer transcriptome revealed a tumor-specific fusion transcript that is preferentially overexpressed in luminal B and metastatic breast cancers and has been shown to increase aggressiveness of luminal breast cancer cells. This fusion also appears to activate a chain of signaling proteins that play a critical role for cancer cell to disseminate and colonize distant organs. To date, this fusion remains the most frequently expressed tumor-specific fusion transcript reported in luminal breast tumors. Importantly, breast cancer cells overexpressing this fusion transcript show markedly increased sensitivity to trametinib, the first FDA approved oral MEK inhibitor used for treating melanoma. This discovery suggests a new paradigm that non-traditional molecular events may be accountable for more aggressive and metastatic breast cancers and are a promising target for treating these deadly tumors.
Applications
· Identification of patients at high risk of distant relapse
· Using MEK inhibitors to prevent and treat breast cancer metastasis in a substantial population of breast cancer patients.
· Personalized management of breast cancer patient cohorts with this specific fusion transcript
Advantages
· Potential to screen primary breast cancer patients for those who need more aggressive treatment and monitoring at an early stage
· Ability to select patients for adjuvant trametinib treatment in combination with standard therapies
· Screen for metastatic breast cancer patients who may benefit from including trametinib in their standard treatment regimens
Invention Readiness
In vitro data
IP Status
https://patents.google.com/patent/US20230340607A1
