Identifying effective methods for targeting cancer stem cells which play a significant role in breast cancer recurrence and metastasis.

Impact

Despite advances in the early detection and treatment of breast cancer, many patients will experience a recurrence, sometimes years after the treatment of their primary cancer. Dr. Clarke's laboratory was the first to identify breast cancer stem cells (CSCs) as major contributors to metastasis—the spread of breast cancer to distant sites. CSCs are also potential drivers of recurrence because of their ability to survive cancer therapy and lie dormant for many years. CSCs are a minor population within tumors but eliminating them may be required to prevent cancer from returning. Dr. Clarke and his team’s work focuses on identifying new therapeutic targets that will specifically eliminate breast CSCs, as well as biomarkers to signal which patients will require adjuvant therapy to prevent breast cancer recurrence. 

Progress Thus Far

A major challenge in developing therapies targeting CSCs is that they are very similar to normal stem cells. Hence, new treatments must be specific to the CSCs to avoid serious side effects. Dr. Clarke’s team developed a method to distinguish CSCs from normal cells, and subsequently identified 40 different stem cell targets that could be used to design therapies for triple-negative breast cancer (TNBC) tumors, which are highly resistant to current therapies. They also identified a CSC-specific gene that appears to regulate tumor stem cell survival and is critical for the establishment, maintenance, and growth of tumors. The team is working on a drug to block this gene and they found a few promising candidates, including a drug that effectively hits its target while not affecting normal cells.  

What’s next

 In the next year, Dr. Clarke’s team will further refine the drug they developed to eradicate CSCs. This will lay the groundwork for further confirmatory studies in the lab before the drug can progress to a clinical trial.