Repurposing a new oral medication for the prevention and treatment of breast cancer
Project Description: The research team, led by Professor Georgia Chenevix-Trench from the QIMR-Berghofer Institute, have discovered a new breast cancer risk gene, called KCNN4. Abnormal expression of the KCNN4 protein in certain subtypes of breast cancer is associated with poor prognosis. The oral medication Senicapoc, which was developed for the treatment of sickle cell anemia, blocks the function of the KCNN4 protein and initial pre-clinical studies show that it can prevent and delay triple negative breast cancer (TNBC) tumour development. Senicapoc has been shown to be safe and well tolerated in humans and this study aims to assess the efficacy of Senicapoc, repurposed for the treatment of TNBC.
Why This Work is Needed: TNBC accounts for 15-20% of all breast cancer cases and has one of the worst prognoses partly due of the lack of hormone receptor expression limiting targeted treatment options. New targeted therapies that can improve survival and/or reduce side effects are greatly needed for this subtype.
Expected Outcomes: The study will yield comprehensive pre-clinical data on the value of Senicapoc for the prevention and/or treatment of TNBC. If proven successful, the drug repurposing opportunity of Senicapoc for breast cancer will reduce the cost of drug development and accelerate translation to the clinic.
The team have discovered a new breast cancer risk gene, KCNN4 that when elevated is associated with poorer outcomes in TNBC. The protein product of KCNN4, a membrane channel, can be targeted by the drug Senicapoc, a drug already investigated for the treatment of sickle cell anemia and has been proven to be safe and well tolerated by humans.
It is believed that Senicapoc partly works by stimulating the immune system. Prof Chenevix-Trench’s study will investigate the mechanism of action, to determine whether the drug works directly on the cancer cells, or on the immune system more broadly. This will also open doors to see whether it can be used in conjunction with other immunotherapies for more effective treatment of hard-to-treat subtypes such as triple negative breast cancer (TNBC).
Senicapoc has the ability to cross from the bloodstream into the brain, meaning that it may also be effective for brain metastases.
Finally, Senicapoc could be an effective preventative (prophylactic) medication, taken by women with BRCA1 and BRCA2 mutations. This could replace the current first-line risk reduction medication tamoxifen, which has some side effects, providing these high-risk patients with an additional preventative option.