Researchers at UCLA’s Jonsson Comprehensive Cancer Center have developed a gene-based imaging system to target castration resistant prostate cancers (CRPCs), potentially allowing oncologists to find and treat metastases faster.
Castration resistant prostate cancer becomes resistant to androgen deprivation therapy—currently the most effective treatment for prostate cancer—and will progress within 12 to 18 months after hormone treatment no longer works, according to the lead author of a recent study published online Sept. 21 in Cancer Research, a peer-reviewed journal of the American Association for Cancer Research. In their study, investigators show that robust PET imaging using “reporter” genes correctly identified metastases in nine out of nine animals.
“Anytime you can detect cancer earlier, the chances of more effective control of the cancer increase and the outcomes for patients are better,” said lead researcher Lily Wu, MD, PhD, UCLA pharmacology, in a statement. “Unfortunately, there is little that can be done to treat castration resistant prostate cancer once it has spread. In our study, we focused on finding ways to image these advanced metastatic prostate cancers accurately.”
Lily Wu’s team used “control switches” of genes that are active only in CRPC and linked the molecular switches to a “reporter” gene that can be easily imaged. The prostate-specific enhancing sequence (PSES) drives the expression reporter genes which glow under bioluminescent or PET scanning.
“The engineered system exhibits greatly elevated transcriptional activity, androgen-independency and strong prostate cancer specificity, verified in cell culture and pre-clinical mouse models,” said Ziyue Karen Jiang, a senior doctoral student in pharmacology, who is supported by a Jonsson Cancer Center fellowship. “These advantageous features of the system elicit superior gene expression capability for castration resistant prostate cancer in comparison to the other systems, which are driven by androgen-dependent promoters.”
Additionally, the PSES system allowed researchers to accurately detect bony metastasis of prostate cancer that grew in the leg of a mouse, while traditional imaging methods were unable to. To study the system's effectiveness, researchers injected prostate cancer cell into mice, let them grow into tumors, and then injected the “reporter genes.” The system identified the cancer, and correctly identified two out of nine mice in which the tumor did not grow.
“In the battle against advanced prostate cancer, there is an urgent and unmet need for a selective imaging modality. The transcription-based molecular imaging approach is particularly advantageous in its ability to be tailored to the molecular and genetic alterations in cancer,” the study authors wrote.