Triple negative breast cancer (TNBC), which accounts for 10-20% of all breast cancers, lacks any of the receptors that are commonly found in breast cancer. Because hormone therapy and other drugs rely on these receptors for effective treatment, TNBC is usually treated with chemotherapy only. Recent genomic sequencing studies have revealed a lack of TNBC-specific mutations. Identifying genetic targets for TNBC could give patients with this form of breast cancer a brighter future and a better shot at recovery.
Description
While the complexity of genomic rearrangements in this cancer has obscured the role that gene fusions play in the pathology of TNBC, researchers at the University of Pittsburgh identified 99 recurrent gene fusions, 57% of which are cryptic adjacent gene rearrangements (AGRs). The most frequently occurring AGRs were preferentially found in the more aggressive forms of breast cancers that lacked well-defined genetic targets; one was found exclusively in TNBC and TNBC tumors with this fusion gene exhibited aggressive histopathological features such as gross necrosis and high tumor grade. This fusion gene was also shown to endow resistance to paclitaxel treatment. RNA- and DNA-based assays for this gene fusion can be used to predict paclitaxel resistance in triple negative breast cancer and allow treatment providers to quickly pivot to alternative treatment options, sparing the patient from the unnecessary and unpleasant side effects of chemotherapy, in addition to serving as a target for novel therapeutics.
Applications
· Detecting a gene fusion unique to triple negative breast cancer and indicative of resistance to paclitaxel
Advantages
· No genetic targets for triple negative breast cancer have previously been identified
Invention Readiness
In vitro data
IP Status
https://patents.google.com/patent/US20230323463A1Related Publication(s)
Lee, S., Hu, Y., Loo, S. K., Tan, Y., Bhargava, R., Lewis, M. T., & Wang, X.-S. (2020). Landscape analysis of adjacent gene rearrangements reveals BCL2L14–ETV6 gene fusions in more aggressive triple-negative breast cancer. Proceedings of the National Academy of Sciences, 117(18), 9912–9921. https://doi.org/10.1073/pnas.1921333117
