Chemoresistance in Ovarian Cancer: Prospects for New Drugs

Abstract

: This review focuses on conventional treatment overview, signaling pathways and various reasons for drug resistance with understanding novel methods that can lead to effective therapies. Ovarian cancer is amongst the most common gynecological and lethal cancers in women from the age of 20-60. The survival rate is limited to 5 years due to diagnosis in subsequent stages with reoccurrence of tumor and resistance of chemotherapeutic. The recent clinical trails use combinatorial treatment of carboplatin and paclitaxel on ovarian cancer after cytoreduction of tumor. Predominantly patients are responsive initially to therapy and later develop metastases due to drug resistance. Chemotherapy also leads to drug resistance causing enormous variations at cellular level. Multifaceted mechanisms like drug resistance are associated with number of genes and signaling pathways that process the proliferation of cells. Reasons for resistance include epithelial-mesenchyme, DNA repair activation, autophagy, drug efflux, pathway activation, and so on. Determining the routes on molecular mechanism that target chemoresistance pathways are necessary for controlling the treatment and understanding efficient drug targets can open light on improve therapeutic outcomes. Most common drug used for ovarian cancer is Cisplatin, which activates various chemoresistance pathways ultimately causing drug resistance. There have been substantial improvements in understanding the mechanisms of cisplatin resistance or chemo sensitizing cisplatin for effective treatment. Using therapies with combination that involve phytochemical or novel drug delivery system involving the phytochemicals would be a novel treatment in cancer. Phytochemicals are plant-derived compounds that exhibit anticancer, anti-oxidative, anti-inflammatory properties that minimalize side effects exerted from chemotherapeutics.

Anticancer effects of natural phytochemicals in anaplastic thyroid cancer (Review)

“…The anticancer effects of phytochemicals in ATC cells, including cell growth inhibition, suppression of angiogenesis, and autophagy modulation, promotion of apoptosis cell cycle arrest, and ROS activation are presented in Table I. Phytochemicals are generally considered to have the ability to reduce ROS activity in other cancers (87)(88)(89). It is unusual for phytochemicals to have the capacity to increase the activation of ROS in ATC cells.…”

miR-4461 Regulates the Proliferation and Metastasis of Ovarian Cancer Cells and Cisplatin Resistance

“…Moreover, PTEN siRNA could eliminate the distinct proliferation capacity or metastasis ability between miR-4461 overexpression OC cells and control cells. Acquired cisplatin resistance is a serious problem for the therapy of OC patients (8,24). miRNAs actually participated in the regulation of tumorigenesis and drug resistance in OC (11,25).…”

Revisiting therapeutic strategies for ovarian cancer by focusing on redox homeostasis (Review)

“…Polyphenols and flavonoids, such as resveratrol, genistein, curcumin, and quercetin, maintain the balance of antioxidant systems by scavenging ROS ( 100 – 103 ). Furthermore, preclinical studies showed that these antioxidant phytochemicals inhibit human cancers, including ovarian cancer, by anticancer activities, including anti-angiogenic, anti-proliferative, anti-inflammatory, and pro-apoptotic properties ( 100 – 103 ). The positive effects of antioxidant therapy have been reported in in vitro and in vivo animal studies.…”

“…Polyphenols and flavonoids, such as resveratrol, genistein, curcumin, and quercetin, maintain the balance of antioxidant systems by scavenging ROS (100)(101)(102)(103). Furthermore, preclinical studies showed that these antioxidant phytochemicals inhibit human cancers, including ovarian cancer, by anticancer activities, including anti-angiogenic, anti-proliferative, anti-inflammatory, and pro-apoptotic properties (100)(101)(102)(103). The positive effects of antioxidant therapy have been reported in in vitro and in vivo animal studies.…”