Placentation is a key and tightly regulated process that ensures the normal development of the placenta and fetal growth. Preeclampsia (PE) is a hypertensive pregnancy-related disorder involving about 5–8% of all pregnancies and clinically characterized by de novo maternal hypertension and proteinuria. In addition, PE pregnancies are also characterized by increased oxidative stress and inflammation. The NRF2/KEAP1 signaling pathway plays an important role in protecting cells against oxidative damage due to increased reactive oxygen species (ROS) levels. ROS activate NRF2, allowing its binding to the antioxidant response element (ARE) region present in the promoter of several antioxidant genes such as heme oxygenase, catalase, glutathione peroxidase and superoxide dismutase that neutralize ROS, protecting cells against oxidative stress damages. In this review, we analyze the current literature regarding the role of the NRF2/KEAP1 pathway in preeclamptic pregnancies, discussing the main cellular modulators of this pathway. Moreover, we also discuss the main natural and synthetic compounds that can regulate this pathway in in vivo and in vitro models.

Among gynaecologic malignancies, ovarian cancer is one of the most dangerous, with a high fatality rate and relapse due to the occurrence of chemoresistance. Many researchers demonstrated that oxidative stress is involved in tumour occurrence, growth and development. Nuclear factor erythroid 2-related factor 2 (NRF2) is an important transcription factor, playing an important role in protecting against oxidative damage. Increased levels of Reactive Oxygen Species (ROS) activate NRF2 signalling, inducing the expression of antioxidant enzymes, such as haem oxygenase (HO-1), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), that protect cells against oxidative stress. However, NRF2 activation in cancer cells is responsible for the development of chemoresistance, inactivating drug-mediated oxidative stress that normally leads to cancer cells’ death. In this review, we report evidence from the literature describing the effect of NRF2 on ovarian cancer, with a focus on its function in drug resistance, NRF2 natural and synthetic modulators and its protective function in normal ovarian preservation.

Ovarian cancer is one of the most dangerous gynecologic cancers worldwide and has a high fatality rate due to diagnosis at an advanced stage of the disease as well as a high recurrence rate due to the occurrence of chemotherapy resistance. In fact, chemoresistance weakens the therapeutic effects, worsening the outcome of this pathology. Solute Carrier Family 7 Member 11 (SLC7A11, also known as xCT) is the functional subunit of the $X_c^{-}$ system, an anionic L-cystine/L-glutamate antiporter expressed on the cell surface. SLC7A11 expression is significantly upregulated in several types of cancers in which it can inhibit ferroptosis and favor cancer cell proliferation, invasion and chemoresistance. SLC7A11 expression is also increased in ovarian cancer tissues, suggesting a possible role of this protein as a therapeutic target. In this review, we provide an overview of the current literature regarding the role of SLC7A11 in ovarian cancer to provide new insights on SLC7A11 modulation and evaluate the potential role of SLC7A11 as a therapeutic target.

Ovarian cancer is one of the most dangerous gynecologic malignancies showing a high fatality rate because of late diagnosis and relapse occurrence due to chemoresistance onset. Several researchers reported that oxidative stress plays a key role in ovarian cancer occurrence, growth and development. The NAD(P)H:quinone oxidoreductase 1 (NQO1) is an antioxidant enzyme that, using NADH or NADPH as substrates to reduce quinones to hydroquinones, avoids the formation of the highly reactive semiquinones, then protecting cells against oxidative stress. In this review, we report evidence from the literature describing the effect of NQO1 on ovarian cancer onset and progression.

CD93 (also known as complement protein 1 q subcomponent receptor C1qR1 or C1qRp), is a transmembrane glycoprotein encoded by a gene located on 20p11.21 and composed of 652 amino acids. CD93 can be present in two forms: soluble (sCD93) and membrane-bound (CD93). CD93 is mainly expressed on endothelial cells, where it plays a key role in promoting angiogenesis both in physiology and disease, such as age-related macular degeneration and tumor angiogenesis. In fact, CD93 is highly expressed in tumor-associated vessels and its presence correlates with a poor prognosis, poor immunotherapy response, immune cell infiltration and high tumor, node and metastasis (TNM) stage in many cancer types. CD93 is also expressed in hematopoietic stem cells, cytotrophoblast cells, platelets and many immune cells, i.e., monocytes, neutrophils, B cells and natural killer (NK) cells. Accordingly, CD93 is involved in modulating important inflammatory-associated diseases including systemic sclerosis and neuroinflammation. Finally, CD93 plays a role in cardiovascular disease development and progression. In this article, we reviewed the current literature regarding the role of CD93 in modulating angiogenesis, inflammation and tumor growth in order to understand where this glycoprotein could be a potential therapeutic target and could modify the outcome of the abovementioned pathologies.