A case report of androgen receptor inhibitor therapy in recurrent high-grade serous ovarian cancer

Limaye, Sewanti; Kumar, Prashant; Pragya, Ramya; Sambath, Janani; Patil, Darshana; Srinivasan, Ajay; Apurva, Sachin; Srivastava, Navin; Patil, Sanket; Patil, Revati; Datta, Vineet; Akolkar, Dadasaheb; Datar, Rajan

doi:10.18632/oncotarget.27809

Cited by 3 publications

(1 citation statement)

References 25 publications

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“…We used synthetic androgen, R1881 in our co-culture study to test the adhesion of fallopian tube cells to the ovary since the ovary expresses aromatase and could metabolize testosterone to estrogen. Bicalutamide, an anti-androgen, was not consistently successful in treating ovarian cancer in early clinical trials, although second generation enzalutamide is now being evaluated in phase II clinical trials [ 50 , 51 ]. The effects of bicalutamide on reducing ovarian cancer cell proliferation are less significant after treatment with chemotherapeutic due to reduced levels of AR [ 49 ]; therefore, the use of anti-androgen should be considered based on expression of AR and may be more impactful prior to other chemotherapy or as cancer prevention.…”

Section: Discussionmentioning

confidence: 99%

Increased Local Testosterone Levels Alter Human Fallopian Tube mRNA Profile and Signaling

Russo

Cain

Jackson-Bey

et al. 2023

Cancers

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Fallopian tube epithelium (FTE) plays a critical role in reproduction and can be the site where High Grade Serous Ovarian Carcinoma (HGSOC) originates. Tumorigenic oviductal cells, which are the murine equivalent of human fallopian tube secretory epithelial cells (FTSEC), enhance testosterone secretion by the ovary when co-cultured with the ovary, suggesting that testosterone is part of the signaling axis between the ovary and FTSEC. Furthermore, testosterone promotes proliferation of oviductal cells. Oral contraceptives, tubal ligation, and salpingectomy, which are all protective against developing ovarian cancer, also decrease circulating levels of androgen. In the current study, we investigated the effect of increased testosterone on FTE and found that testosterone upregulates wingless-type MMTV integration family, member 4 (WNT4) and induces migration and invasion of immortalized human fallopian tube cells. We profiled primary human fallopian tissues grown in the microfluidic system SOLO-microfluidic platform –(MFP) by RNA sequencing and found that p53 and its downstream target genes, such as paired box gene 2 (PAX2), cyclin-dependent kinase inhibitor 1A (CDK1A or p21), and cluster of differentiation 82 (CD82 or KAI1) were downregulated in response to testosterone treatment. A microfluidic platform, the PREDICT-Multi Organ System (PREDICT-MOS) was engineered to support insert technology that allowed for the study of cancer cell migration and invasion through Matrigel. Using this system, we found that testosterone enhanced FTE migration and invasion, which was reversed by the androgen receptor (AR) antagonist, bicalutamide. Testosterone also enhanced FTSEC adhesion to the ovarian stroma using murine ovaries. Overall, these results indicate that primary human fallopian tube tissue and immortalized FTSEC respond to testosterone to shift expression of genes that regulate invasion, while leveraging a new strategy to study migration in the presence of dynamic fluid flow.

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Section: Discussionmentioning

confidence: 99%

Increased Local Testosterone Levels Alter Human Fallopian Tube mRNA Profile and Signaling

Russo

Cain

Jackson-Bey

et al. 2023

Cancers

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Antineoplastics

2021

Reactions Weekly

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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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A case report of androgen receptor inhibitor therapy in recurrent high-grade serous ovarian cancer

Cited by 3 publications

References 25 publications

Increased Local Testosterone Levels Alter Human Fallopian Tube mRNA Profile and Signaling

Increased Local Testosterone Levels Alter Human Fallopian Tube mRNA Profile and Signaling

Antineoplastics

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

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