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Personalized Medicine for Triple Negative Breast Cancer Could Become Reality Following New Biomarker Discovery

Breast cancer is the most frequently diagnosed cancer type and the second leading cause of cancer death in women worldwide. Triple negative breast cancer (TNBC), the most aggressive form of the disease, accounts for 10-20% of all breast cancer cases and cannot be treated with some of the most effective targeted therapies available for other breast cancer cases. A new study has identified a biomarker that could be utilized to develop personalized therapies for TNBC patients.

Treatment decisions in breast cancer are based upon the histology of the tumor focusing on the status of the main biomarkers of response. This classification divides breast cancer into a hormone dependent subtype – including tumors that are positive for the estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) – and a hormone independent subtype, which include TNBC. Most breast cancers associated with mutation of the gene BRCA1 are TNBC.

Patients diagnosed with hormone dependent breast cancer receive hormonal therapies such as such as Tamoxifen or aromatase inhibitors - or treatments that target HER2 receptors, including Herceptin® (trastuzumab), a HER2 monoclonal antibody. However, TNBC does not express ER or PRs, and does not have an excess of the HER2 protein on the cell surfaces. This makes these tumors insensitive to some of the most effective targeted therapies available for breast cancer, hence more difficult to treat.

Currently, a combination of surgery, chemotherapy and radiotherapy is the most common treatment strategy for the condition. However, due to the aggressive phenotype of TNBC, especially those harboring BRCA mutations, the initial response is often followed by disease relapse or metastasis. Metastatic breast cancer currently remains incurable, and has a poor 5-year overall survival rate, making TNBC an area of high unmet need for patients.

The investigation, and in some cases clinical trials, of new treatments such as DNA damaging chemotherapy agents including poly(ADP-ribose) polymerase (PARP) inhibitors, novel microtubule inhibitors, and other targeted therapies in TNBC is still ongoing. As there is an ever increasing number of treatment options emerging, relevant biomarkers need to be identified, as well as combination therapies, to enable patient stratification for personalized care, which will ultimately lead to improved clinical outcomes.

A recent study published in Breast Cancer Research by Sam Thiagalingam, associate professor at Boston University School of Medicine (BUSM) and colleagues reported the discovery of high levels of a molecule called IL13R alpha2 (IL13RA2) on the surface of metastatic or advanced TNBC cells.

The team was able to show that breast cancer patients with high-grade tumors and increased IL13RA2 levels had significantly worse prognosis for metastasis-free survival compared with patients with low expression of the molecule. In addition, they found that patients with a subtype of TNBC characterized by rapid spread to the lungs had high levels of IL13RA2 in their cancer cells.

To gain some insight into the mechanism of action of the newly identified biomarker the BUSM researchers used a mouse model of TNBC with reduced expression of IL13RA2. They found that lowering IL13RA2 slows down tumor growth, and reduce cancer cells spreading to the lungs.

Based on their findings, it is possible to suggest IL13RA2 as an important drug target for personalized treatment of TNBC patients.

Crown Bioscience has a longstanding track record in breast cancer research with a variety of TNBC research platforms available for all stages of drug development including patient derived Xenografts (PDXs), the most translatable models in oncology research, cell line-derived xenografts (CDX), and in vitro services ranging from target validation, drug mechanism of action, assay development, high-throughput drug screening, indication selection, combination treatment screening, to biomarker discovery.

Crown Bioscience can be contacted at busdev@crownbio.com for enquiries about our TNBC models and services or for any other information.

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