A recent study has proposed a new adaptive therapy method that could improve PARP inhibitor maintenance treatment for ovarian cancer. This approach is tailored to each patient, offering a potentially safer and more personalized option. Ovarian cancer is often detected late, making it difficult to treat, and patients tend to develop resistance to traditional treatments quickly. Despite aggressive treatment, the recurrence rates for this cancer remain high, prompting the need for innovative approaches. PARP inhibitors have become a popular treatment option, targeting specific DNA repair processes.Cancer cells have mechanisms to resist treatment, including the use of PARP inhibitors. However, these inhibitors are often limited in their effectiveness due to toxicity and the emergence of drug resistance.
A new study by researchers at Moffitt Cancer Center has introduced an adaptive therapy approach to optimize PARP inhibitor maintenance therapy. This approach offers a more personalized and potentially less toxic treatment option for patients. The study, featured as the cover article of the June 19 issue of Cell Systems, aims to improve the effectiveness of PARP inhibitors, which block a protein that helps repair damaged DNA and prevent cancer cells from repairing themselves.Chemotherapy is used to kill cancer cells, but the traditional method of giving the highest tolerated dose can cause serious side effects and require lowering the dose, which can make the treatment less effective. Researchers at Moffitt Cancer Center used math and lab tests to compare different dosing methods. They found that adjusting the dose based on how the tumor is responding is better than skipping doses. Adaptive therapy personalizes the treatment to the tumor’s behavior, so the drug levels can be adjusted based on the patient’s specific disease.”Our research indicates that adjusting the dosage of medication, rather than skipping doses, can reduce the amount of drug needed while still keeping it effective,” explained Alexander Anderson, Ph.D., the study author and chair of the Integrated Mathematical Oncology Department at Moffitt. “This method can decrease toxicity and possibly slow down the development of resistance.”
To observe how ovarian cancer cells responded to various treatment schedules, the team used time-lapse microscopy. Their model showed that continuously adjusting the dosage effectively controlled the tumor with a much lower amount of medication compared to traditional methods. In vivo experiments corroborated these findings.The results have been confirmed and show that the adaptive approach is practical. The research is ongoing to further validate and improve adaptive therapy strategies. Maximilian Strobl, Ph.D., who led the project, emphasized the unique opportunity to conduct in vitro experiments to calibrate and test mathematical models. Strobl also highlighted the importance of integrating theory and experiments closely, stating that it was a rewarding experience. He believes that this iterative and interdisciplinary approach is crucial.A multidisciplinary approach is essential for creating better cancer treatment schedules, according to the researchers. The National Cancer Institute and the Moffitt Center of Excellence for Evolutionary Therapy provided funding for their work.
