Thanks to work done at Institute Curie by a team led by Fatima Mechta-Grigoriou, Inserm Research Director, it is now possible to identify, among women with aggressive ovarian cancer, those who could benefit from a promising targeted therapy.
Métastase tumorale dans l’ovaire © Inserm/Evrard, Gilles.
The Stress and Cancer team (an Inserm/Institut Curie team designated by the French National Cancer League), directed by Fatima Mechta-Grigoriou (photo, right), has just taken a major step toward identifying women with an aggressive form of ovarian cancer who are likely to benefit from targeted therapy in the form of a MEK inhibitor.
Finding the Achilles heel of ovarian tumour cells
Moreover, BRAF activates the MEK signalling pathway involved in the development of low-grade ovarian tumours. MEK inhibitors have therefore been proposed as a possible therapeutic solution for these cancers.“75% of ovarian cancers are high grade, i.e. highly aggressive. The mutation profile differs between low- and high-grade tumours,” explains Virginie Mieulet (photo, left), post-doctoral fellow and co-author of this work. “For example, alterations in the KRAS/BRAF oncogenes are present in 70% of less aggressive tumours, but in only 1% of aggressive tumours.”
“The MAP3K8 protein might serve as a biomarker for identifying patients likely to benefit from a therapy based on MEK inhibition,” adds Fatima Mechta-Grigoriou, Inserm Research Director, “especially since it can be quite simply detected from a tissue section by our physician pathologist colleagues, who, incidentally, have helped us greatly in this work.”
While clinical trials are already underway to assess MEK inhibitors in low-grade ovarian cancers, everything seems to point to the interest of developing a clinical trial in women with high-grade ovarian cancer overexpressing MAP3K8, to evaluate the efficacy of this targeted therapy, in addition to the conventional chemotherapies.
 Because of the key role of the MEK signalling pathway in carcinogenesis—activation is observed in 30% of cancers—MEK inhibitors constitute a promising therapeutic approach. Clinical trials are currently underway for several tumour locations (skin melanoma, intestinal tumours, thyroid cancer, etc.).
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MAP3K8/TPL-2/COT is a potential predictive marker for MEK inhibitor treatment in high-grade serous ovarian carcinomas Tina Gruosso 1,2 , Camille Garnier 1,2, Sophie Abelanet 1,2, Yann Kieffer 1,2, Vincent Lemesre 1,2, Dorine Bellanger 3,2, Ivan Bieche 4, Elisabetta Marangoni 5, Xavier Sastre-Garau 6, Virginie Mieulet 1,2, § and Fatima Mechta-Grigoriou 1,2, § 1 Stress and Cancer Laboratory, Institut Curie, 26, rue d’Ulm, 75248 Paris 2 Inserm, U830, Paris, F-75248 3 Genomics and Biology of the Hereditary Breast Cancers, Institut Curie, 26, rue d’Ulm, 75248 Paris 4 Department of Pharmacogenomics, Institut Curie, 26, rue d’Ulm, 75248 Paris 5 Laboratory of Precinical Investigation, Translational Research Department, Institut Curie, 26, rue d’Ulm, 75248 Paris 6 Department of Pathology, Institut Curie, 26, rue d’Ulm, 75248 Paris