Polo Like Kinase 1 (PLK1) inhibitor as a potent treatment strategy for SCLC patients with a specific TP53 mutation.
- A personalized cell therapy for recurrent SCLC cases.
- Higher efficiency in TP53 mediated PLK1 inhibition to control carcinoma.
- PLK1, a predictive biomarker for SCLC diagnosis.
Lung cancer is the most common form of cancer in terms of incidence and number of deaths. Out of 30,000 newly diagnosed patients of SCLC in the US, more than 80% will die from their disease within 2 years of diagnosis and less than 5% will survive to 5 years post diagnosis. In spite of response to frontline chemotherapy drugs, there is a recurrence of disease, which is often resistant to further treatment, leading to early death of patients. Today, topotecan is the only approved treatment for relapsed SCLC. Consequently, the relapsed disease represents an area of great unmet need and an opportunity to develop novel treatments in SCLC.
Emory University inventors have identified repurposed PLK1 inhibitors for SCLC treatment and a companion diagnostic for SCLC patients with a specific TP53 mutation that will respond to the inhibition of PLK1 with higher efficiency. TP53 gene functions as repressor of PLK1 expression. Inactivating alterations in these genes, especially the TP53 gene, is expected to result in high PLK1 levels. The inventors identified the TP53 gene mutation could be used as a predictive biomarker to identify patients with high levels of PLK1 and predict sensitivity to PLK1 inhibitors. Inhibitors against this protein may prove to be a successful therapy to overcome the recurrence and drug-resistance of SCLC.
- In-vitro preclinical screening in a panel of well-annotated SCLC cell lines using investigational and approved targeted agents.
- In-vivo anticancer efficacy was assessed using athymic nu/nu mice.