Simultaneous expression of steroid sulfatase and androgen receptor reduced overall survival of patients with epithelial ovarian tumors

Calvillo-Robledo, Argelia; Pedernera, E.; Morales-Vásquez, Flavia; Pérez-Montiel, Delia; Gómora, María J.; Almaraz, Miguel Ángel; Graue, Paulina García de Alba; Rendón, Elizabeth; López-Basave, Horacio Noé; Quintanar‐Stephano, Andrés; Méndez, C.

doi:10.1186/s13048-021-00840-x

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…A limitation of the present study is the number of tumors which are evaluated; consequently, the influence of confounding factors could be underestimated. However, the hazard ratio for 17β-HSD1-positive expression is independent of age and FIGO stage, two variables that affect overall survival ( 39 ). Moreover, the present results suggest that estrogens are involved in the progression of epithelial ovarian tumors and favor better patient overall survival in serous epithelial ovarian tumors.…”

Section: Discussionmentioning

confidence: 99%

17β-hydroxysteroid dehydrogenase type 1 improves survival in serous epithelial ovarian tumors

Pedernera,

Morales-Vásquez,

Gómora

et al. 2023

Endocrine Connections

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The incidence of ovarian cancer has been epidemiologically related to female reproductive events and hormone replacement therapy after menopause. This highlights the importance of evaluating the role of sexual steroid hormones in ovarian cancer by the expression of enzymes related to steroid hormone biosynthesis in the tumor cells. This study was aimed to evaluate the presence of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), aromatase and estrogen receptor alpha (ERα) in the tumor cells and their association with the overall survival in 111 patients diagnosed with primary ovarian tumors. Positive immunoreactivity for 17β-HSD1 was observed in 74% of the tumors. In the same samples, aromatase and ERα revealed 66% and 47% positivity, respectively. No association was observed of 17β-HSD1 expression with the histological subtypes and clinical stages of the tumor. The overall survival of patients was improved in 17β-HSD1-positive group in Kaplan–Meier analysis (P = 0.028), and 17β-HSD1 expression had a protective effect from multivariate proportional regression evaluation (HR = 0.44; 95% CI 0.24–0.9; P = 0.040). The improved survival was observed in serous epithelial tumors but not in nonserous ovarian tumors. The expression of 17β-HSD1 in the cells of the serous epithelial ovarian tumors was associated with an improved overall survival, whereas aromatase and ERα were not related to a better survival. The evaluation of hazard risk factors demonstrated that age and clinical stage showed worse prognosis, and 17β-HSD1 expression displayed a protective effect with a better survival outcome in patients of epithelial ovarian tumors.

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Section: Discussionmentioning

confidence: 99%

17β-hydroxysteroid dehydrogenase type 1 improves survival in serous epithelial ovarian tumors

Pedernera,

Morales-Vásquez,

Gómora

et al. 2023

Endocrine Connections

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“…Although OC is more traditionally associated with estrogen and progesterone receptors, different other studies have highlighted AR involvement in OC. AR expression has been observed in various subtypes of OC and its activation has been linked to tumor growth and poor prognosis suggesting that targeting AR signaling, especially with AR antagonists such as enzalutamide, might represent a potential therapeutic strategy for OC [134][135][136]. In this context, abiraterone, a potent inhibitor of the enzyme CYP17A1, plays a crucial role in androgen biosynthesis and has been explored as a therapeutic agent in AR-driven cancers.…”

Section: Hormonal Regulation and Its Implications For Dna Damage And ...mentioning

confidence: 99%

Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients

De Lazzari,

Opattova,

Arena

2024

J Exp Clin Cancer Res

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Over the last few decades, the incidence of urogenital cancers has exhibited diverse trends influenced by screening programs and geographical variations. Among women, there has been a consistent or even increased occurrence of endometrial and ovarian cancers; conversely, prostate cancer remains one of the most diagnosed malignancies, with a rise in reported cases, partly due to enhanced and improved screening efforts.Simultaneously, the landscape of cancer therapeutics has undergone a remarkable evolution, encompassing the introduction of targeted therapies and significant advancements in traditional chemotherapy. Modern targeted treatments aim to selectively address the molecular aberrations driving cancer, minimizing adverse effects on normal cells. However, traditional chemotherapy retains its crucial role, offering a broad-spectrum approach that, despite its wider range of side effects, remains indispensable in the treatment of various cancers, often working synergistically with targeted therapies to enhance overall efficacy.For urogenital cancers, especially ovarian and prostate cancers, DNA damage response inhibitors, such as PARP inhibitors, have emerged as promising therapeutic avenues. In BRCA-mutated ovarian cancer, PARP inhibitors like olaparib and niraparib have demonstrated efficacy, leading to their approval for specific indications. Similarly, patients with DNA damage response mutations have shown sensitivity to these agents in prostate cancer, heralding a new frontier in disease management. Furthermore, the progression of ovarian and prostate cancer is intricately linked to hormonal regulation. Ovarian cancer development has also been associated with prolonged exposure to estrogen, while testosterone and its metabolite dihydrotestosterone, can fuel the growth of prostate cancer cells. Thus, understanding the interplay between hormones, DNA damage and repair mechanisms can hold promise for exploring novel targeted therapies for ovarian and prostate tumors.In addition, it is of primary importance the use of preclinical models that mirror as close as possible the biological and genetic features of patients’ tumors in order to effectively translate novel therapeutic findings “from the bench to the bedside”.In summary, the complex landscape of urogenital cancers underscores the need for innovative approaches. Targeted therapy tailored to DNA repair mechanisms and hormone regulation might offer promising avenues for improving the management and outcomes for patients affected by ovarian and prostate cancers.

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“…Studies on the alteration of agonist/antagonist properties of anti-androgens due to different AR mutations have stimulated the search for new drugs that inhibit AR signal transduction [23,24]. It has been seen how mutations in the AR gene and splicing variants can lead, in most cases, to increased cellular aggressiveness in hormone-dependent cancers such as prostate, breast, and ovary [12,[25][26][27][28][29][30][31]. All the AR domains can undergo mutations.…”

Section: Androgen Receptor (Ar)mentioning

confidence: 99%

Role of the Androgen Receptor in Gender-Related Cancers

et al. 2023

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The androgen receptor (AR) is expressed in many cell types, and its related signaling is widely investigated in hormone-dependent cancers such as prostate and breast. The significance of the AR, however, has been detected even in other cancers, including gastric, bladder, kidney, lung, hepatic, and pancreatic, in which growth and spreading are not strictly or notoriously dependent on sex steroid hormone action. The incidence and mortality of these cancers are, however, somewhat related to gender and, specifically, are higher in men than in women, with the ratio reaching 3–4:1 for bladder cancer. This direct correlation between cancer incidence, mortality, and gender makes sex one of the most important risk factors for these cancers and has incited investigation about the role of sex steroid receptors and their activating hormones in gender-related cancers. In these cancers, the AR is often expressed and seems to play a pivotal role in different processes contributing to cancer onset and progression such as growth, spreading, and epithelial to mesenchymal transition (EMT). This manuscript will offer an overview of the role of the AR in many cancers of the respiratory and gastrointestinal systems wherein its role has been at least partially analyzed. Understanding the role of the AR in these tumors could help us to identify a new biomarker for early diagnostic guidance and to develop better therapeutic approaches by directly targeting the AR or its downstream signaling in individual cells of hormone-related cancers at different stages.

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Simultaneous expression of steroid sulfatase and androgen receptor reduced overall survival of patients with epithelial ovarian tumors

Cited by 8 publications

References 23 publications

17β-hydroxysteroid dehydrogenase type 1 improves survival in serous epithelial ovarian tumors

17β-hydroxysteroid dehydrogenase type 1 improves survival in serous epithelial ovarian tumors

Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients

Role of the Androgen Receptor in Gender-Related Cancers

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