UGA researchers have found a way to enhance chemotherapy’s cancer-killing powers, bringing science one step closer to a more complete cancer treatment.
Chemotherapy’s ultimate goal is to destroy a person’s cancer, but one common type of the treatment known as antimicrotubule chemotherapy has the tendency to let cancer cells slip through at the exact time that it’s supposed to kill them during the cell division phase known as mitosis.
These dividing cells leave through a process known as mitotic slippage. It’s here that UGA researchers have targeted their studies—in understanding how mitotic slippage occurs and how to prevent it. According to the study published Oct. 24 in the Journal of Cell Biology, they found a drug combination that caused 100 percent mitotic cell death, thereby significantly improving the killing efficiency of antimicrotubule chemotherapy drugs.
The drug combination they discovered “could revolutionize chemotherapy by dramatically improving one of the main classes of chemotherapy drugs,” said the study’s senior author, Edward Kipreos, a professor in the Franklin College of Arts and Sciences cellular biology department.
To get to that treatment, they first uncovered the cause of mitotic slippage: the action of the protein complex CRL2-ZYG11. Inactivating this protein complex can significantly improve antimicrotubule chemotherapy’s ability to kill mitotic cells.
By combining conventional antimicrotubule drugs with a new drug called MLN4924 that targets all CRL complexes, the researchers were able to achieve complete mitotic cell death during testing. MLN4924 has undergone phase I clinical trials, meaning that it has been evaluated for safety, to determine a safe dosage range and to identify side effects.
The paper focuses on new insights into the regulation of mitosis, primarily on the inactivation of cyclin B1-CDK1, an enzyme complex that is essential for mitosis. Because cyclin B1 activity promotes the mitotic program, cyclin B1 must be degraded during mitosis to allow cells to exit mitosis. Previously, the understanding was that cyclin B1 is targeted for degradation solely by the action of the anaphase-promoting complex/cyclosome, or APC/C, ubiquitin ligase.
