Inflammation and ovarian cancer

Epithelial ovarian cancer (EOC) is a highly lethal gynecological cancer for which overall prognosis has remained poor over the past few decades. A number of theories have been postulated in an effort to explain the etiology of EOC. Noteworthy, these theories likely are not mutually exclusive, as they all converge more or less on the role of inflammation in promoting ovarian tumorigenesis and cancer progression. The tumor milieu in which ovarian carcinoma develops has been described as one enriched with a broad spectrum of pro-inflammatory cytokines and chemokines. In particular, several of these cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, produced by tumor itself or/and activated immune cells, besides stimulating cancer cell growth, have been shown to influence clinical disease status and prognosis, by reducing responsiveness to chemotherapy and inducing symptoms such as anorexia, altered energy metabolism, anemia, weight loss, depression and fatigue. Recent data show that cytokine antagonists may have a role to play in the treatment of ovarian cancer. Their action by inhibiting both production and activity of inflammatory cytokines seems to obtain the control of angiogenetic and apoptotic events, the reversal of chemoresistance, the improvement of systemic symptoms and prognosis. In the light of our scientific research and the most recent experimental and clinical advances, our review will discuss the most relevant and recent findings on the role of proinflammatory cytokines in the pathogenesis and prognosis of ovarian cancer and the possible therapeutic implications.