Trovagene’s enzyme inhibitor PCM-075 increases the punch of the prostate cancer therapy Zytiga (abiraterone), preclinical-trial studies show.
PCM-075 is a selective polo-like kinase 1 (PLK1) inhibitor. It inhibits a protein called PLK1, whose levels are particularly high in cancer cells and which doctors have associated with poor patient outcomes. Studies have shown that inhibiting PLK1 triggers the death of tumor cells.
Zytiga is the world’s leading androgen deprivation therapy for metastatic castration-resistant prostate cancer, or mCRPC. It decreases levels of male hormones associated with the cancer.
A castration-resistant prostate cancer in one in which the level of a biomarker of the disease known as PSA continues to rise, or new symptoms appear, after doctors treat the cancer with radiation therapy or surgery. A metastatic cancer is one that has spread to another part of the body.
The studies that Trovagene has conducted on PCM-075 suggest that it can increase Zytiga’s effectiveness.
“The synergy observed when we combined PCM-075 with abiraterone appears to work through a novel mechanism that may modulate a signalling pathway previously unknown to be associated with this combination,” Dr. Mark Erlander, Trovagene’s chief scientific officer, said in a press release.
“This unique combination appears to enhance the PCM-075 mechanism of action of arresting cells during mitosis, with subsequent tumor cell death,” Erlander added. Mitosis is the process by which a single cell divides into two cells. Arresting cells during mitosis means preventing them from dividing.
Scientists have reported that PCM-075 increases the punch of more than 10 chemotherapies and targeted therapies used against several cancers. Trovagene’s findings indicate that Zytiga has now joined this list.
Patients with castration-resistant prostate cancer resist androgen-deprivation therapies like Zytiga. Their PSA levels continue to rise, their tumors continue to grow, and the tumors spread.
PCM-075 may delay the resistance and slow the progression of mCRPC, researchers said.
“We are encouraged by the preclinical data of PCM-075 in mCRPC,” said Bill Welch, Trovagene’s chief executive officer. “We previously completed a Phase 1 trial in metastatic solid tumor cancers, which provided a recommended Phase 2 dose and dosing schedule for PCM-075 in a combination regimen. We are working closely with key investigators to develop a Phase 2 clinical trial protocol with oral dosing of PCM-075 and abiraterone.”