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Triple negative breast cancer (TNBC) involves any breast cancer that does not express the genes for estrogen, progesterone and epidermal growth factor receptor 2. An estimated 1 million cases of breast cancer are diagnosed annually worldwide and of these, 170,000 are of TNBC phenotype. While the overall cancer rates are down ~25% in the past 20 years, death rates due to TNBC remain unchanged, making it a single deadliest threat to women's health worldwide. In terms of TNBC disease pathology, the infiltration of distant organs is the most common cause of treatment failure, disease recurrence and eventual death.
Unfortunately, the only available treatment options for TNBCs patients include surgical removal of tumor followed by intensive and cytotoxic chemotherapy, mainly due to lack of targeted therapies. While many patients respond to these treatments, the disease prognosis is very poor and up to 85% of recurrent cancer patients develop chemoresistance, metastasis and eventually die. A major limitation in developing an effective treatment for TNBC is the lack of targetable genetic determinants of metastasis.
We have recently uncovered a new function for a breast cancer oncogene called TRIM37 that enables tumor cells to resist chemotherapeutic as well as metastatic stress. High-TRIM37 induces gene expression changes that are characteristic of a metastatic phenotype and inhibition of TRIM37 substantially reduces the TNBC cell survival in animal models. Most importantly, we have engineered a targeted therapy that combines lipid-based nanoparticles and immunotherapy to selectively deliver a TRIM37 inhibitor to cancer cells, but not to surrounding healthy cells. We show that this strategy effectively reduces lung metastatic lesions and significantly increases survival, thereby establishing TRIM37 as a new therapeutic target for treating metastatic TNBC. If successful, this new delivery platform can also be used to selectively and effectively deliver chemotherapeutic drugs to cancer cells and minimize side effects associated with cancer treatment.
You can read the full article in the November 2020 issue of the American Association for Cancer Research Journal (Volume 80, Issue 21).*
*Please note that you must have a subscription to view the article in its entirety or purchase access to the journal.
You can see more from Dr. Bhatnagar in the news stories below.