Newly Developed Drug Could Improve Cancer Chemotherapy
A new study conducted by researchers from the South Carolina College of Pharmacy reports a new class of drugs that would diminish the adverse effects of chemotherapy. Chemotherapy does not only kill cancerous cell but also kills healthy cells.
Early results show that the new class of drugs is applicable to many types of cancer and could potentially increase patients recovery after the end of chemotherapy. Researchers note that the new drugs could be used in future treatment schemes for Alzheimer’s or other age-related diseases.
“Conventional anticancer drugs, while essential for current cancer therapy, have side effects that can damage healthy cells and cause them to promote the growth of surviving cancer cells. We needed to find a way to interrupt that process, said Igor Roninson, the leader of the research group.
Previous studies have shown that current drugs damage both the cancerous cells and the normal tissue of the patient, thus causing many drug-related changes, the most important being senescence. The aging of cells (senescence) is the result of chromosomal changes that occur along with the aging process. However, many of the current anticancer drugs have been shown to cause an earlier aging in cells. Researchers have shown that both senescent cells and other damaged cells produce different molecules and proteins that support the further growth of a tumor. Furthermore, these molecules and proteins appear to be implicated in diseases such as arthritis and Alzheimer’s.
The secretory activities of these senescent cells has been proven in precedent studies, but without giving a practical method to block them. Igor Roninson’s team of researchers reports the development of a chemical that inhibits the secretory activity of senescent cells. This new chemical is called Senexin A. The team reported their findings in the Proceedings of the National Academy of Sciences. The inhibiting effect of the new chemical is related to reducing the most important side-effect of chemotherapy.
In one of the experiments, led by study co-author Hippokratis Kiaris, from the University of Athens, Greece, laboratory mice were treated with a common anticancer drug and afterwards were injected with cancerous cells. The results showed that the mice that were pretreated with the common anticancer drug developed tumors faster. Moreover, blood samples from these mice were found to contain high amounts of tumor growth stimulating proteins.
The mice treated with the new chemical, Senexin A, showed a reduced tumor growth and production of proteins that stimulated the growth of the tumor. Simultaneously, the use of Senexin A increased the effectiveness of the anticancer drug.
The newly developed chemical targets CDK8, also known as cyclin-dependent kinase 8, which is a protein kinase. Protein kinases are enzymes that modify proteins by adding phosphate to them. Senexin A is the first chemical that selectively inhibits the activity of CDK8 and CDK19. CDK8 has a role in regulating gene expression, however, it does not have a role in the cell division process.
Precedent studies have shown a link between CDK8 and two types of cancer (melanoma and colon cancer). The research team discovered an important connection between the gene expression of CDK8 and the duration of relapse-free survival in patients suffering from ovarian and breast cancer. Patients with breast cancer that had a minor CDK8 gene expression survived relapse-free almost seven years longer than patients showing a stronger CDK8 gene expression.
The results of this study implicate the CDK8 protein kinase in the production of tumor stimulating proteins, whilst also suggesting that the new class of drugs could bring benefit to multiple types of cancer.