Researchers at GW overcame platinum drug resistance in ovarian cancer by combining JAK2 inhibitor LY2784544 with standard platinum based chemotherapeutics. Doctors commonly prescribe platinum-based drugs, like cisplatin, to treat ovarian cancer. Over time many patients become resistant to the treatment and succumb to the disease. Doctors need new options for effective treatment of platinum resistant cancers.
Our research revealed that constitutive activation of the JAK2-STAT5 pathway causes platinum-resistance. LY2784544, a selective JAK2 inhibitor, re-sensitizes platinum resistant ovarian cancer cells to cisplatin. Nanomolar concentrations of LY2784544 greatly decreased the resistance to cisplatin in cisplatin-resistant ovarian cancer cell lines. LY2784544 also displayed synergism with cisplatin when applied to nonresistant ovarian cancer cells. In vivo, the combination therapy suppressed growth of xenograft Cisplatin-resistant ovarian cancer xenografts.
In addition, the researchers also identified a companion diagnostic for this therapy. The treatment should work best on patients with overactive JAK2/STAT5 pathway, which may be identified by high levels of IL11 Receptor.
Figure: Cisplatin-resistant ovarian cancer xenograft tumor growth is suppressed when treated with a combination of LY2784544 and cisplatin.
Applications:
Advantages:
- Overcomes platinum-based drug resistance
- Synergistic effect of combination therapy
- Companion diagnostic identified
