Research from the Ringshausen group (Haematology, Wellcome-MRC Cambridge Stem Cell Institute and CRUK Cambridge Centre) and collaborators has shown that PKC inhibitors can be re-purposed to directly target tumour stroma cells.
The team has identified a stromal cell–autonomous signaling pathway, which contributes to drug resistance of malignant B cells and show that protein kinase C (PKC)–β–dependent signals from bone marrow–derived stromal cells markedly decrease the efficacy of cytotoxic therapies. They then demonstrated that this signalling pathway can be antagonised with existing small molecule PKC inhibitors. Simultaneously targeting cancer cells with chemotherapy and stroma cells with PKC-inhibitors is synergistic and improves survival rates in genetic and patient derived disease models.
The research, published in Science Translational Medicine, has the potential to significantly enhance current treatments and extend life expectancy for many patients with different types of leukaemia and lymphomas, including chronic lymphocytic leukaemia, acute lymphoblastic leukaemia, and mantle cell lymphoma. Plans for a clinical trial based on this research are in development.