Abstract
Simple SummaryAround 4% of cancer deaths in the world was associated to ovarian cancer (OC), making it the eighth most common cause of death in women. Increasing evidence suggests that ion channels play critical role in the main stages of OC process, including proliferation, migration and metastasis. The aim of this review was to provide an updated description of the current knowledge concerning ion channels’ involvement in OC, with a particular emphasis of their role in the acquired chemoresistance. Importantly, ion channels might represent new molecular targets for the development of OC treatment, exploiting the availability of the well-known ion channel-targeting drugs.Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment.
Highlights
A variety of ion channels are remarkably expressed in human Ovarian cancer (OC) cells and tissues, where they are involved in the development of various malignant behaviors, including proliferation, migration, invasion, and apoptosis resistance
Accumulating data have revealed that the aberrant expression of ion channels in OC greatly contribute to the main hallmarks of OC process, from initial proliferation to metastasis to chemoresistance
The T-type Ca2+ channels, for example, are overexpressed in ovarian cancer where they are involved in tumor growth and its chemoresistance to platinum-based drugs [89]
Summary
The disease is characterized by few and unspecific symptoms such as abdominal pain, swelling, or nonspecific gastrointestinal symptoms, which can be confused with other nonmalignant conditions [8] This means that the majority of women are not diagnosed until the disease has reached an advanced stage, associated with a poor diagnosis, when the tumor has spread to the upper abdomen, reaching lymphatic vessels and brain. The discovery of targets with important functions in OC progression and prognosis might facilitate the development of novel therapeutic strategies In this line, recent studies have demonstrated the contribution of ion channels in the progression of various tumors, including breast cancer, prostate cancer, and colon cancer [12]. Growing evidence has suggested that ion channel expression/activity could play a role in the pathophysiology of OC and could represent new targets for treatment [15].
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