SOME forms of ovarian cancer have a weakness that could be exploited by a new class of therapies. The discovery is Italian and comes from the Mario Negri – Irccs Pharmacological Research Institute, thanks to a study supported by the AIRC Foundation for Cancer Research, the results of which are published in Cancer Research. The study calls into question the mitochondria, the “power plants” of cells: in practice, the researchers observed that ovarian tumors with high levels of two proteins (PGC-1Ī± and PGC-1Ī²), essential in regulating the activity of mitochondria, are sensitive to a new inhibitor that targets these organelles.
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Mitochondria “in the crosshairs”
The researchers focused on studying the Oxphos process (oxidative phosphorylation), which is the process that allows cellular respiration that occurs in the mitochondria, the organelles that produce the energy necessary for cells to grow and reproduce. āInhibiting the ability of mitochondria to produce energy – explains Raffaella Giavazzi, coordinator of the study – therefore means preventing cancer cells from growing and proliferating, and if the cells are no longer able to produce energy, they face certain death. For this reason, in recent years several studies have suggested interfering with the function of mitochondria in targeted anticancer therapies “.
I study
The research of the Negri Institute, conducted in cultured cells and on laboratory animals with ovarian cancer, has in fact shown that by blocking the metabolic process in the mitochondria with an inhibitor (indicated with the initials IACS-010759), it is possible to control the growth of the carcinoma. However, ovarian cancers are not all the same and this therapeutic approach would be suitable only in some cases. āWe have found that Oxphos inhibition is not equally effective on all types of ovarian cancer. This benefit is in fact related to the expression of the two main proteins that regulate mitochondrial activity “, explain Carmen Ghilardi, first author of the article, and Maria Rosa Bani, head of the Tumor Metastasis Therapy laboratory at the Negri Institute:” In practice, by damaging the mitochondria and causing a decrease in cellular functions that depend on energy, it is possible to delay the progression of the disease, with more efficacy in those ovarian tumors with high levels of PGC-1Ī± / Ī² “.
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Just as the inhibitor is not effective on tumors that express low levels of PGC-1Ī± / Ī², it seems to have no effect even on normal cells: a first confirmation comes from the results obtained on laboratory animals in which no toxicity was highlighted, despite the treatments have continued for a long time. The relevance of these findings was also confirmed by analyzing data from a sample of tumors from ovarian cancer patients. āThe research – says Giavazzi – has shown that in the sample analyzed, about 25% of patients have high levels of the two proteins that regulate the activity of mitochondria. At this point – he concludes – the next step will be to understand if the results obtained in the preclinical models are transferable to those suffering from this type of ovarian cancer “.
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The study takes steps forward in the study of treatments for one of the most difficult cancers to treat, for which there is no screening test and which does not even have specific symptoms. In fact, in 75-80% of cases, the diagnosis comes when the disease is at an advanced stage and has already given rise to metastases.
Photo: Cell and mitochondria (in red). Credits: National Cancer Institute via Unsplash