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Cancer is a disease characterised by important metabolic alterations. Not only these adaptative changes give higher proliferative capacity to cancer cells, but they also contribute to higher resistance to chemotherapeutic agents. The research group led by Dr. Jos Carlos Fernndez-Checa in the Institut d'Investigacions Biomdiques de Barcelona of the CSIC (IIBB-CSIC), a centre linked to the Institut d'Investigacions Biomdiques August Pi i Sunyer (IDIBAPS), is centred in the mitochondrion and its role in programmed cell death or apoptosis. The mitochondrion is the organelle in charge of the cell's respiration and of energy generation to satisfy important metabolic functions, which are altered in cancer. In an article published in Cancer Research (68(13):5246-56) with Joan Montero and Albert Morales as first signatories and Ana Colell as co-director of the study, IIBB-CSIC-IDIBAPS researchers describe how the increase of cholesterol in the mitochondrial membrane plays a key role in the resistance to cytotoxic agents acting via mitochondrion, including doxorubicin, a common drug in chemotherapy. This research has been developed in the framework of the Centre of Network Biomedical Research on Hepatic and Digestive diseases (CIBERehd).
Hepatocarcinoma is the most frequent form of hepatic cancer. It has a high mortality rate due to, among other causes, the lack of an effective treatment and due to its high resistance against the current chemotherapy strategy. In order to improve the quality of treatments, it is important to identify the strategies permitting the cell to avoid chemotherapy's toxicity. The supraphysiological level of mitochondrial cholesterol in hepatocarcinoma and in other cancers is well known, but its role in the mitochondrial regulation of cellular death and resistance to chemotherapy was not known.
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IDIBAPS - Institut d'Investigacions Biomdiques August Pi i Sunyer