Modeling Responses to Intermittent ADT in Patients With Advanced Prostate Cancer
Posted: Friday, May 8, 2020
Researchers from the Moffitt Cancer Center have developed a simulation model suggesting that intermittent androgen-deprivation therapy (ADT) may be useful in certain patients with advanced prostate cancer. This model further showed that treatment strategies may be optimized based on patients’ prostate-specific antigen (PSA) dynamics. Heiko Enderling, PhD, of the H. Lee Moffitt Cancer Center and Research Institute,Tampa, Florida, and colleagues published their work in Nature Communications.
“Continuous treatment, by maximally selecting for resistant phenotypes and eliminating other competing populations, may actually accelerate the emergence of resistant populations—a well-studied evolutionary phenomenon termed competitive release,” said Dr. Enderling in an Moffitt press release.
The team developed a mathematical model of prostate cancer stem cells, nonstem prostate cancer cells, and serum PSA concentration based on a study in which 79 men completed at least one cycle of intermittent ADT. Their model is built upon the hypothesis that prostate cancer stem cells contribute to differences in both tumors between patients and treatment failure. As such, the model simulates PSA dynamics and highlights enrichment of prostate cancer stem cells during treatment as a possible mechanism of treatment resistance.
The simulated prostate cancer stem cell proliferation pattern was correlated with longitudinal serum PSA levels in 70 of the 79 patients studied. Stem cells were highly associated with intermittent resistance to ADT, leading to changing levels of PSA. The model simulations were able to predict patient-specific evolution of resistance with an overall accuracy of 89%. In addition, this model could predict which patients may benefit from alternative therapies.
“This ability to learn from early treatment cycles and predict subsequent responses adds an essential degree of personalization and flexibility to a cancer treatment protocol,” commented Dr. Enderling.
Disclosure: For full author disclosures, visit www.nature.com.
