Targeting the Glia-Induced CDK5 Expression That Enforces Antigenic Escape of Brain Metastasis
Abstract
Breast cancer is the most common invasive cancer in women. Overall statistics tell us that this disease has a reasonably good prognosis, with 5-year relative survival rate of around 90%. However, patients with triple negative breast cancer (TNBC) have a significantly worse prognosis (TNBC means that the three most common types of receptors known to fuel most breast cancer growth are not present in the tumor). In addition, patients with advanced disease, that is, when a cancer that began in the breast has spread to another part of the body, have much less favorable outcome: only 15 out of 100 women (15%) will survive their cancer for 5 years or more after they are diagnosed. Advanced TNBC is not curable; nonetheless, it can be controlled for several years with appropriate treatment. Breast cancer spreads, or metastasizes, to quite a few organs, including the brain. Patients with brain metastasis have a particularly poor prognosis with only 20% surviving 1 year after diagnosis. Unfortunately, effective therapies for such individuals are lacking, mainly because we do not know much about how to cure tumors in the brain. So, brain metastasis is a very dangerous consequence of breast cancer, and more fundamental research should be done to advance our understanding of this disease, with the final aim to improve quality of life and survival of this group of patients. Dr. Arseniy Yuzhalin is a young but experienced cancer researcher who graduated from Oxford University, England. His major interest and long-term career goal is curing brain metastasis, a devastating consequence of breast cancer that dramatically impacts on people s lives. Dr. Yuzhalin and his mentor, Professor Dihua Yu, found that a molecule called CDK5, which normally regulates cell division, is supporting TNBC brain metastasis growth and enables TNBC cells to escape from the immune system. CDK5 is overexpressed in 30%-35% of breast cancer patients. Dr. Yuzhalin proposes to block CDK5 using an established drug, approved by the Food and Drug Administration (i.e., safe to use), specifically in women with TNBC breast cancer brain metastasis. There are no safety risks at all, as the drug is already under trial to treat other conditions, but Dr. Yuzhalin first needs to learn more about the exact role of CDK5 in brain metastasis by utilizing state-of-the-art science techniques applied to multiple genetically engineered cancer cell lines as well as clinically relevant patient-derived xenograft (PDX) mouse models of TNBC brain metastasis. If his experiments indeed prove that the CDK5 inhibition drug reduces TNBC metastasis outgrowth, Dr. Yuzhalin s research team plans to rapidly organize its clinical trial at their home institution, MD Anderson Cancer Center, which has a large clinical base and strong support team of clinical doctors and managers. Such a clinical trial may take 2-4 years, and, if successful, the drug can be included in established clinical guidelines and recommendations within about 1 year. Taking into account the time required for laboratory experiments, survival of patients with brain metastasis from breast cancer can be substantially improved in the next 6-8 years. Therefore, the results from this study may lead to dramatic positive changes in the quality of life of women suffering from breast cancer brain metastasis. Additionally, male patients with metastatic breast cancer may also benefit from the above-mentioned therapy. Eventually, Dr. Yuzhalin hopes to cure brain metastasis and thus reduce breast cancer mortality by establishing novel therapeutic regimens based on targeting CDK5.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210064
Entities
People
- Arseniy E. Yuzhalin
Organizations
- The University of Texas MD Anderson Cancer Center
- United States Army