Over the past decade, kinase inhibitors have remarkably improved the treatment of cancer and have radically changed the course of history by improving cancer cure rates. When kinases are active they fuel cancer cell growth and promote the spread of cancer to different parts of the body. The key is finding the essential kinase that is responsible for the growth of each cancer type and then blocking its activity. By determining which kinase is the Achilles’ heel for a particular type of cancer, we can deliver personalized, targeted therapies with better treatment results. 

Approximately 170,000 cases of Triple-Negative Breast Cancer (TNBC) are diagnosed every year worldwide and is one of the most difficult breast cancer subtypes to treat due to lack of effective therapies.  Out of all the 518 human kinases, RSK1 and RSK2 have proven to be critical to the survival of TNBC patients.  Our work centers on creating patented cancer RSK inhibitors and companion diagnostics for cancers, initially in breast cancer, but with future plans to expand our patented novel approach to treating blood, brain, ovarian, lung, skin, prostate, colon, head and neck cancers.

Evaluation of RSK inhibition with small interfering RNAs using high-content screening (HCS), a program Dr. Dunn established at BC Children’s and Women’s hospitals, enabled researchers to identify novel biomedical targets for therapy. In a secondary HCS screen, RSK inhibitors were compared to a library of 129 drugs that are already in clinical trials, and were conspicuous in killing more cancer cells then most other drugs in that screen. Importantly, inhibiting RSK2 eliminates TNBC cells completely, including cancer stem cells, which give rise to cancer recurrence, but not the healthy cells.  By targeting these cells, there is the potential to cure TNBC.


 

Our work focuses on developing novel drugs around kinases, specifically p90 ribosomal S6 kinases (RSK), which we have led the field in establishing as a molecular target for cancer.


There are four types of RSK involved in cancer, known as RSK1-4, and each type has a unique role in the development of the disease. RSK1 is responsible for cancer cell invasion and is an important driver in the spread of cancer. RSK2 controls cancer cell growth, and RSK3 and RSK4 are associated with drug resistance. 

RSK1 and RSK2 have been proven critical to the survival of patients with Triple-Negative Breast Cancer (TNBC), one of the most difficult breast cancer subtypes to treat due to lack of effective therapies. More than 400,000 women have been diagnosed with TNBC worldwide. Inhibiting RSK2 eliminates TNBC cells completely, including cancer stem cells, which give rise to cancer recurrence. By targeting these cells with RSK inhibitors, there is the potential to cure TNBC.

RSK inhibitors are also candidates for improving other forms of breast cancer. For example, our research demonstrates that tumors with amplified Her-2 rely on the RSK pathway to mount resistance to Herceptin. Herceptin is a kinase inhibitor that has markedly improved the treatment of breast cancer for patients who developed tumors with Her-2 amplifications. However, for many patients Herceptin is effective initially but then the cancer cells activate the RSK pathway and they are no longer sensitive to Herceptin. Our research shows that RSK inhibitors can overcome Herceptin resistance and thus can be used to improve the treatment of Her-2 positive breast cancers.

RSK1 and RSK2 are also drug targets for medulloblastoma, the most common type of pediatric brain tumor. In addition, RSK inhibitors can be used to improve the treatment of skin, ovarian, prostate, lung, head and neck, colon, kidney and pancreatic cancers.