AsianScientist (Oct. 5, 2017) – In a study published in the journal the Proceedings of the National Academy of Sciences, scientists in Japan and the US have discovered that the anti-parasite drug, ivermectin, can be used in the treatment of ovarian cancer.
Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer-related deaths in women, with approximately 239,000 women being diagnosed with the disease each year. The outlook upon diagnosis is grim, hence there is a need to discover new ways to treat EOC.
In this study, a team of researchers in Japan and the US performed a screen for new drug target genes for EOC, which involved two in vivo screenings—one shRNA based and the other CRISPR/Cas9 based. Several targets were found, including the proto-oncogene ERBB2, but because there were already drugs that target ERBB2 in clinical use, the team decided to focus on the gene with the second highest rank in the screening, KPNB1.
Osaka University Gynecologist Dr. Michiko Kodama, who was the first author of the study, confirmed that KPNB1 has features consistent of an oncogene, finding that its overexpression significantly accelerated EOC cell proliferation and survival, while its inhibition induced programmed cell death. Adding to the likelihood that this gene has a role in EOC, Kodama also found that the prognosis for EOC patients was poorer in individuals whose tumors had higher KPNB1 expression.
The researchers noted that the anti-parasite drug, ivermectin, is known to exert therapeutic effect by binding to KPBN1. They thus treated EOC cells with ivermectin and found that it caused programmed cell death in EOC cells. If the KPNB1 activity was already artificially suppressed in the cancer cells, ivermectin failed to work, indicating that ivermectin’s therapeutic effect was specifically enacted through KPBN1. Moreover, ivermectin had a synergistic effect when combined with paclitaxel, the currently preferred drug for EOC treatment.
“Ivermectin inhibits importin-mediated nuclear transport. KPNB1 is a member of the importin family,” explained Kodama. “However, we still do not understand the molecular mechanisms for its synergistic effect with paclitaxel.”
Nonetheless, because ivermectin is already approved to treat parasitic infections in patients, the researchers expect that the process to gain regulatory approval for its use in EOC treatment will be significantly cheaper and faster compared to untested drug compounds.
The article can be found at: Kodama et al. (2017) In vivo Loss-of-function Screens Identify KPNB1 as a New Druggable Oncogene in Epithelial Ovarian Cancer.
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Source: Osaka University; Photo: Shutterstock.
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