Problem

Dedifferentiated liposarcomas (DDLPS) are aggressive soft tissue sarcomas with limited effective treatment options and a dismal prognosis. Current therapies often fail due to tumor resistance, poor specificity, and toxicity. The aggressive clinical behavior of LPS and its resistance to chemotherapy have been linked to the aberrant activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. However, previous attempts to target AKT clinically have not yielded successful outcomes. There is a need for targeted therapies for LPS that can inhibit tumor growth and metastasis with minimal side effects

Solution

Researchers at The Ohio State University have discovered how the phosphorylation of the transcription elongation factor IWS1 by AKT contributes to LPS tumor biology and have identified novel compounds designed to inhibit IWS1 from in silico screen of commercially available FDA-approved drugs. By targeting IWS1, specifically disrupting the formation of the IWs1/Spt6 complex, they aim to disrupt the process that promotes the maintenance of cancer stem cells and contributes to a “metastable” cell phenotype, characterized by mesenchymal/epithelial plasticity. The lead compounds were tested in the DDLPS cell lines, where they significantly reduced cancer cell proliferation, migration and invasiveness, with IC50 values in the low micromolar range

Applications

• Treatment of cancer, especially DDLPS and other soft tissue sarcomas. Potential use in other solid tumors where IWS1 plays a role in cancer biology
• Combination therapies with existing drugs, such as doxorubicin

Advantages

• Target specificity: the therapy focuses on IWS1, reducing off-target effects
• Reduced metastasis: the treatment inhibits cell migration and epithelial-mesenchymal transition, therefore reducing the likelihood of metastasis
• Versatility: the drugs selected from the screening can be formulated in various delivery methods, such as oral and injectable
• Potential for combination therapies: the compounds are supposed to work well with existing chemotherapeutics
• Improved outcomes: targeting the AKT/IWS1 axis may offer a novel therapeutic strategy to combat tumor heterogeneity and resistance in LPS

Seeking opportunities for out-licensing and collaboration