Researchers discovered how AB Science’s therapy masitinib — a veterinary medicine sold as Kinavet in the U.S. — acts to re-sensitize drug-resistant tumor cells to the anti-cancer treatment Gemzar (gemcitabine).
The discovery could lead to better treatments for diseases where nucleoside analogues like Gemzar are used as therapy, such as in some viral diseases and cancers.
The results from the preclinical study were published in the article, “Dual protein kinase and nucleoside kinase modulators for rationally designed polypharmacology,” in the journal Nature Communications.
The researchers found that masitinib acts on an enzyme called human deoxycytidine kinase (dCK) and activates it. In turn, dCK modifies nucleoside analogues, Gemzar among them, making them more potent.
Masitinib can promote the activity of nucleoside analogue agents in fighting cancer. Therefore, it can potentially be used to reduce the toxicity of dCK-dependent drugs by maintaining drug effectiveness at lower doses or by counteracting drug resistance in tumors.
“These findings represent a novel mechanism of action for masitinib that is of relevance to its oncology development program,” Patrice Dubreuil, director of research at the INSERM Center for Cancer Research of Marseille and senior author of the study, said in a press release. “This property of masitinib is of potential clinical benefit through either reducing toxicity of dCK-associated therapeutic agents by maintaining therapeutic efficiency at lower doses, or by amplifying the effectiveness of such agents in order to counteract drug resistance. Furthermore, because nucleoside-like drugs are among the most important therapeutic agents currently used to treat tumors and viral diseases, this discovery could also be of benefit for a variety of other diseases.”
“The findings reported in this article provide additional justification for the development of masitinib in combination with nucleoside-like anticancer drugs such as gemcitabine,” said professor Olivier Hermine, president of the Scientific Committee at AB Science.
A Phase 2 trial (NCT02490488) of masitinib in the treatment of ovarian cancer is now active. The trial will enroll 68 patients with advanced ovarian cancer who progressed following first-line platinum-based chemotherapy and test if masitinib plus Gemzar is better at improving patients’ survival than Gemzar alone.
In addition, a Phase 3 clinical program of the masitinib-Gemzar drug combination in relapsed or refractory advanced/metastatic epithelial ovarian and pancreatic cancer, and T-cell lymphoma is underway.