Repurposing an arthritis drug for the treatment of metastatic triple negative breast cancer

Project Description: The spread of breast cancer to the brain is a major cause of mortality for patients with triple negative breast cancer (TNBC). In this study Prof Kum Kum Khanna (QIMR Berghofer Medical Research Institute) will examine whether Auranofin, a drug proven to be safe for the treatment of rheumatoid arthritis and can cross the blood-brain barrier, can be repurposed for the treatment of metastatic TNBC. Auranofin will be tested in combination with other FDA approved anti-cancer drugs known to reach the brain to identify new combination therapies for the treatment for metastatic TNBC.

Why the Work is Needed: Triple negative breast cancers (TNBCs) are associated with a high risk of early recurrence often spreading to distant organs (metastasis). The brain is a common site of triple negative breast cancer metastasis, and this disease is largely incurable with patients experiencing very poor survival outcomes. A common problem for the treatment of cancers that spread to the brain is the lack of drugs that can effectively cross the blood-brain barrier and reach cancer cells in the brain. Hence, there is an urgent unmet need to identify new effective treatments for TNBC patients with brain metastasis.

Expected Outcomes: Successful outcome of this study will generate data showing that auranofin can be used in combination with other drugs that can penetrate into the brain new combination therapies for metastatic TNBC cancer in the brain. Since auranofin is already approved for use in people, the successful outcomes of this study will provide the rationale for the design and initiate a clinical trial for TNBC patients with brain metastasis.

Project Details

Triple negative breast cancers (TNBCs) accounts for approximately 15% of breast cancer cases and represent a major clinical challenge due to the lack of estrogen, progesterone and HER receptors as they do not respond to hormonal and anti-HER2 therapies. TNBCs also have a high risk of recurrence and are highly metastatic with treatments largely limited largely to surgery, radiotherapy, and chemotherapy, and while effective for some patients, many patients relapse after treatment with metastasis to brain occurring in up to half of these patients.

Previous work from Prof Khanna and her team at QIMR Berghofer Medical Research Institute have found that metastatic TNBC brain cancer has elevated levels of a protein called thioredoxin reductase. Thioredoxin reductase protects cancer cells from the brain’s immune system. This study will repurpose a drug called auranofin, that blocks the activity of this protein and is safe and approved for use in patients by the United States by the Food and Drug Administration (FDA). Importantly this drug can cross the blood-brain barrier, a common obstacle for treating brain metastatic disease.

With this NBCF support, the team will use clinically relevant TNBC pre-clinical models to test auranofin in combination with other FDA approved anti-cancer drugs known to reach the brain. Outcomes from this study will provide compelling evidence for the effectiveness of a combination therapy including Auranofin for the treatment of metastatic TNBC cancer in the brain, revolutionizing treatment and extending the life of patients with breast cancer with this disease.

This grant is aligned with the generous donations raised by the Mother’s Day Classic Foundation (MDC).