Nasr on the Need for Preclinical Models of Prostate Cancer Dormancy

Mostafa Nasr, PhD candidate, Moffitt Cancer Center, discusses the development of novel preclinical models of prostate cancer dormancy, and the significance of these outcomes may have on future research in metastatic prostate cancer.

Recurrent metastatic prostate cancer commonly manifests in the skeleton and can occur several years after the primary tumor develops, Nasr begins. This period of time between the development of the primary tumor and subsequent metastasis is known as cancer dormancy. The molecular mechanisms responsible for entry to and exit from tumor dormancy have not yet been elucidated, in part due to a lack of preclinical and in vitro models within prostate cancer, Nar explains.

To address this unmet need, a novel in vitro model of prostate cancer dormancy using human cell lines was developed alongside a preclinical mouse model, Nasr says. Preliminary data derived from these models implicates PRDM16 as a key regulator of entry into tumor dormancy. RNA sequencing and bioinformatic analysis showed that PRDM16 levels were found to be elevated during entry into tumor dormancy in both models. Genetic silencing of PRDM16 consequently reduced the ability of prostate cancer cells to enter dormancy in vitro. Notably, cells entering dormancy formed long-term clusters that could be reawakened through the addition of serum. Moreover, PRDM16 was shown to upregulate anti-apoptotic proteins, such as BCL2, while inhibiting pro-apoptotic proteins, such as BIM and NOXA.

These models were found to effectively represent the prostate cancer dormancy phenotype, Nasr continues. Investigations of other molecular involved in tumor dormancy using a mouse model are currently ongoing, Nasr says. Once proof of concept is confirmed for this model, clinical trials could be conducted to investigate or devise newer targeted approaches, he adds. Agents that trigger apoptosis in cancerous cells may also be investigated using these models, Nasr concludes.