Advantages
- A new diagnosis/treatment method for platinum-resistant ovarian cancer, for which there was no clear definition or treatment.
- Repurposing of JAK inhibitors
- Companion diagnosis
Background and Technology
Platinum resistance (PltR) to platinum-based anticancer drugs is the most serious issue for ovarian cancer (OvCa) patients, but the definition of PltR is vague and the mechanism is unknown.
We analyzed mRNA and miRNA in cancer tissues and ascites extracellular vesicles (EVs) of patients with PltR-OvCa. As a result, we found significant activation of the JAK/STAT pathway and increased expression of multiple miRNAs in cancer tissues and EVs of patients with PltR-OvCa.
In OvCa cell lines, overexpression overexpression of selected miRNAs promoted JAK/STAT expression and significantly enhanced cisplatin-resistance. Furthermore, administration of a JAK inhibitor, which is used clinically as a treatment for rheumatoid arthritis, showed a growth-suppressive effect on cisplatin-resistant OvCa cell lines, and tumor-bearing mouse models transplanted with the same cell lines. Furthermore, the combined administration of JAK inhibitors and cisplatin showed synergistic effects in suppressing the growth of cisplatin-resistant OvCa cell lines.
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Reference
- Patent pending (unpublished yet)
Principal Investigator
Akira Yokoi (Department of Obstetrics and Gynecology, Nagoya University Hospital)
Current Stage and Next Step
- The efficacy of JAK-targeted therapy with companion diagnostics for platinum-resistant ovarian cancer has been confirmed through animal experiments.
- We are seeking collaborative partners for the repurposing development of JAK inhibitors as a treatment for platinum-resistant ovarian cancer. We are also looking for development partners for companion diagnostics.
- This laboratory has many research results such as biomarkers related to ovarian cancer and gynecological diseases, and collaboration is possible.
Project.BK-04663