RESUMO
Ovarian cancer is the most lethal gynecological neoplasm, and epithelial ovarian cancer (EOC) accounts for 90% of ovarian malignancies. The 5-year survival is less than 45%, and, unlike other types of cancer, the proportion of women who die from this disease has not improved in recent decades. Nerve growth factor (NGF) and tropomyosin kinase A (TRKA), its high-affinity receptor, play a crucial role in pathogenesis through cell proliferation, angiogenesis, invasion, and migration. NGF/TRKA increase their expression during the progression of EOC by upregulation of oncogenic proteins as vascular endothelial growth factor (VEGF) and c-Myc. Otherwise, the expression of most oncoproteins is regulated by microRNAs (miRs). Our laboratory group reported that the tumoral effect of NGF/TRKA depends on the regulation of miR-145 levels in EOC. Currently, mitochondria have been proposed as new therapeutic targets to activate the apoptotic pathway in the cancer cell. The mitochondria are involved in a myriad of functions as energy production, redox control, homeostasis of Ca+2, and cell death. We demonstrated that NGF stimulation produces an augment in the Bcl-2/BAX ratio, which supports the anti-apoptotic effects of NGF in EOC cells. The review aimed to discuss the role of mitochondria in the interplay between NGF/TRKA and miR-145 and possible therapeutic strategies that may decrease mortality due to EOC.
RESUMO
Epithelial ovarian cancer (EOC) is one of the deadliest gynaecological malignancies. The late diagnosis is frequent due to the absence of specific symptomatology and the molecular complexity of the disease, which includes a high angiogenesis potential. The first-line treatment is based on optimal debulking surgery following chemotherapy with platinum/gemcitabine and taxane compounds. During the last years, anti-angiogenic therapy and poly adenosine diphosphate-ribose polymerases (PARP)-inhibitors were introduced in therapeutic schemes. Several studies have shown that these drugs increase the progression-free survival and overall survival of patients with ovarian cancer, but the identification of patients who have the greatest benefits is still under investigation. In the present review, we discuss about the molecular characteristics of the disease, the recent evidence of approved treatments and the new possible complementary approaches, focusing on drug repurposing, non-coding RNAs, and nanomedicine as a new method for drug delivery.