Uveal melanoma: a promising avenue for treating metastatic forms
Uveal melanoma is the most common form of eye cancer in adults, with 500 to 600 new cases diagnosed in France every year. As long as the tumour is localised, the treatments currently available - including surgery, protontherapy and curietherapy - limit the risk of local recurrence in ten years to 5%. However, as soon as the disease has spread through metastasis, usually to the liver, which happens to one patient in three, the prognosis is compromised. “So far no treatment has proven truly effective in terms of survival to treat metastatic forms of the disease,” explains Dr Sophie Piperno-Neumann, clinical oncologist at Institut Curie and a specialist in this pathology. Although therapeutic options targeting PKC have generated some optimism, this is not enough.” The doctors and researchers at Institut Curie therefore had the idea to combine therapies targeted on other pathways, often disrupted in this type of cancer, with a PKC inhibitor (AEB071).
“The result was beyond all of our hopes, since these combinations were effective in the 5 preclinical models representative of the different types of uveal melanoma at our disposal. Two combinations - PKC inhibitor associated with either a p53-MDM2 inhibitor or a mTORC1 inhibitor - seem to be especially promising”, explains Dr Didier Decaudin, clinical oncologist, manager of the preclinical investigation laboratory. These two combinations have proven their effectiveness in cultured cell lines.
“The dual inhibition of PKC and p53-MDM2 or mTORC1 is the most effective of the therapeutic combinations tested on our preclinical models and represents hope for the treatment of metastatic forms of uveal cancer”, adds Dr Sophie Piperno-Neumann. “We now have sufficient evidence to support these combinations to begin clinical trials in patients.”
Find out more
"Dual inhibition of protein kinase C and p53-MDM2 or PKC and mTORC1 are novel efficient therapeutic approaches for uveal melanoma"
Guillaume Carita, Estelle Frisch-Dit-Leitz, Ahmed Dahmani, Chloé Raymondie, Nathalie Cassoux, Sophie Piperno-Neumann, Fariba Némati, Cécile Laurent, Leanne De Koning, Ensar Halilovic, Sebastien Jeay, Andrew Wylie, Caroline Emery, Sergio Roman-Roman, Marie Schoumacher, Didier Decaudin
Oncotarget, 22 mai 2016, DOI: 10.18632/oncotarget.9552