Targeting Metabolic Pathway in Treating Aggressive Prostate Tumors
Posted: Thursday, June 18, 2020
Dominic J. Smiraglia, PhD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, and colleagues have identified a novel drug combination that appeared to effectively target aggressive prostate tumors. The new therapeutic strategy, published in Nature Communications, targets two enzymes in the polyamine catabolic and the methionine salvage pathways. In laboratory tests, the combination therapy appeared to block the growth of prostate tumors, including castration-recurrent prostate cancer.
“The primary problem with prostate cancer therapy is that nearly all men recur after an initial response to androgen-deprivation therapy, leaving patients and clinicians with no more good options,” Dr. Smiraglia stated in a Roswell Park press release. “This new metabolic approach is completely independent of androgen-deprivation therapy. Ultimately, the hope is that it will prevent recurrence during traditional androgen deprivation.”
The research lab previously found that prostate cells are sensitive to metabolic changes related to polyamines and determined that cell metabolism may be driving the clinical setbacks of therapy resistance and metastasis. After observing a high rate of flux through the polyamine biosynthetic and catabolic pathways, the team developed a two-part strategy to target the metabolic processes involved in prostate cancer. The approach first inhibits methylthioadenosine phosphorylase, the rate-limiting enzyme, while simultaneously upregulating spermidine/spermine N1-acetyltransferase. The combination treatment increased apoptosis in radical prostatectomy laboratory samples.
According to the investigators, the two-target approach may also be combined with additional agents, such as docetaxel. “Docetaxel combined with BENSpm [bisethylnorspermine] and MTDIA [methylthio-DADMe-immucillin-A] may be more efficacious in the clinic,” they proposed.
Disclosure: The study authors reported no conflicts of interest.
