Abstract
Ovarian cancer remains the most lethal gynaecological cancer. A better understanding of the molecular pathogenesis of ovarian cancer is of critical importance to develop early detection tests and identify new therapeutic targets that would increase survival. Cancer cells depend on de novo lipid synthesis for the generation of fatty acids to meet the energy requirements for increased tumour growth. There is increasing evidence that lipid metabolism is deregulated in cancers, including ovarian cancer. The increased expression and activity of lipogenic enzymes is largely responsible for increased lipid synthesis, which is regulated by metabolic and oncogenic signalling pathways. This article reviews the latest knowledge on lipid metabolism and the alterations in the expression of lipogenic enzymes and downstream signalling pathways in ovarian cancer. Current developments for exploiting lipids as biomarkers for the detection of early stage ovarian cancer and therapeutic targets are discussed. Current research targeting lipogenic enzymes and lipids to increase the cytotoxicity of chemotherapy drugs is also highlighted.
Highlights
Ovarian cancer is the most lethal gynaecological cancer and ranks as the fourth most common cause of cancer-related death in women in the Western world [1]
These findings indicate that activity of Phospholipase D (PLD) is associated with both constitutive and Lysophosphatidic acid (LPA)-induced LPA production in ovarian cancer cells [70]
Abnormal lipid metabolism plays an important role in the pathogenesis of ovarian cancer
Summary
Ovarian cancer is the most lethal gynaecological cancer and ranks as the fourth most common cause of cancer-related death in women in the Western world [1]. The treatment for advanced ovarian cancer is debulking surgery followed by platinum- and taxane-based chemotherapy This standard treatment results in a complete response rate of 40%–60%; more than 90% of patients relapse after 18 months and, with the emergence of chemoresistance, die from the disease [2]. Cancer cells rely on de novo lipid synthesis for the generation of fatty acids to meet the needs of tumour growth, resulting in specific alterations in different aspects of lipid metabolism. These alterations can influence the availability of structural lipids for the synthesis of membranes, the production and degradation of lipids for energy supply and the abundance of lipids with signalling functions. Research employed to overcome chemotherapy resistance by targeting lipogenic enzymes and lipids to increase the cytotoxicity of chemotherapy drugs is highlighted
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