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Resistance to Therapy in Ovarian Cancers
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Resistance to Therapy in Ovarian Cancers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 March 2024) | Viewed by 7650

Special Issue Editor

Dr. Serena Bonin

E-Mail Website
Guest Editor
DSM-Department of Medical Sciences, University of Trieste, 34149 Trieste, Italy
Interests: high-grade serous ovarian cancers; RNA profiling; RNA analysis; tissue processing; biomarkers

Special Issue Information

Dear Colleagues,

Ovarian cancers encompass a collection of neoplasms with distinct clinical–pathological, molecular features and prognosis. Most of them are epithelial tumors including high-grade serous ovarian cancers (about 70%), endometrioid carcinomas, clear cell carcinomas, mucinous carcinomas, and low-grade serous ovarian cancers. Ovarian cancers are the deadliest tumor of the female reproductive system. They are mostly asymptomatic; consequently, they are usually diagnosed in an advanced stage (FIGO stage III or IV) and characterized by extended intratumor heterogeneity. The mortality rate has not changed in recent decades, and more than 50% of women still die within five years of diagnosis. Cytoreductive surgery followed by adjuvant platinum-based chemotherapy with or without maintenance therapy (bevacizumab or poly adenosine diphosphate ribosepolymerase (PARP) inhibitors) is the standard of care in most cases. Most patients are initially platinum sensitive, but soon after, they relapse. PARP inhibitors (PARPi) benefit patients with homologous recombination deficiency epithelial ovarian cancers by blocking the DNA repair pathways and inducing the apoptosis of cancer cells. However, similar to other chemotherapy agents, PARP inhibitors have different clinical indications and toxicity profiles, and 40–70% of patients experience drug resistance.

This Special Issue of IJMS will highlight the recent advances in understanding drug resistance in ovarian cancers. Experimental papers, up-to-date review articles, and commentaries are all welcome.

Dr. Serena Bonin
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ovarian cancers
  • therapy response
  • biomarkers
  • innovative drugs
  • drug resistance
  • drug metabolism
  • drug delivery
  • platinum-based chemotherapy
  • PARP inhibitors
  • intratumor heterogeneity
  • microenvironment
  • homologous recombination deficiency

Published Papers (3 papers)

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Research

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19 pages, 5593 KiB  
Article
Nanomechanical Characterization of Ovarian Cancer Cell Lines as a Marker of Response to 2c Treatment
by Domenico Tierno, Eros Azzalini, Rossella Farra, Sara Drioli, Fulvia Felluga, Marco Lazzarino, Gabriele Grassi, Barbara Dapas and Serena Bonin
Int. J. Mol. Sci. 2023, 24(8), 7230; https://doi.org/10.3390/ijms24087230 - 13 Apr 2023
Viewed by 1461
Abstract
Epithelial ovarian cancers (EOCs) are a heterogeneous group of tumors with different molecular and clinical features. In past decades, few improvements have been achieved in terms of EOC management and treatment efficacy, such that the 5-year survival rate of patients remained almost unchanged. [...] Read more.
Epithelial ovarian cancers (EOCs) are a heterogeneous group of tumors with different molecular and clinical features. In past decades, few improvements have been achieved in terms of EOC management and treatment efficacy, such that the 5-year survival rate of patients remained almost unchanged. A better characterization of EOCs’ heterogeneity is needed to identify cancer vulnerabilities, stratify patients and adopt proper therapies. The mechanical features of malignant cells are emerging as new biomarkers of cancer invasiveness and drug resistance that can further improve our knowledge of EOC biology and allow the identification of new molecular targets. In this study, we determined the inter and intra-mechanical heterogeneity of eight ovarian cancer cell lines and their association with tumor invasiveness and resistance to an anti-tumoral drug with cytoskeleton depolymerization activity (2c). Full article
(This article belongs to the Special Issue Resistance to Therapy in Ovarian Cancers)
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17 pages, 3132 KiB  
Article
A Regulatory Loop Involving miR-200c and NF-κB Modulates Mortalin Expression and Increases Cisplatin Sensitivity in an Ovarian Cancer Cell Line Model
by Xin Huang, Yichen Yan, Ailing Gui, Shun Zhu, Shi Qiu, Feng Chen, Wen Liu, Ji Zuo and Ling Yang
Int. J. Mol. Sci. 2022, 23(23), 15300; https://doi.org/10.3390/ijms232315300 - 04 Dec 2022
Cited by 2 | Viewed by 1343
Abstract
Ovarian cancer is currently the most lethal gynecological cancer. At present, primary debulking surgery combined with platinum-based chemotherapy is the standard treatment strategy for ovarian cancer. Although cisplatin-based chemotherapy has greatly improved the prognosis of patients, the subsequent primary or acquired drug resistance [...] Read more.
Ovarian cancer is currently the most lethal gynecological cancer. At present, primary debulking surgery combined with platinum-based chemotherapy is the standard treatment strategy for ovarian cancer. Although cisplatin-based chemotherapy has greatly improved the prognosis of patients, the subsequent primary or acquired drug resistance of cancer cells has become an obstacle to a favorable prognosis. Mortalin is a chaperone that plays an important role in multiple cellular and biological processes. Our previous studies have found that mortalin is associated with the proliferation and migration of ovarian cancer cells and their resistance to cisplatin-based chemotherapy. In this study, microRNA (miR)-200b/c downregulated mortalin expression and inhibited the proliferation and migration of the paired cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) epithelial ovarian cancer cell lines. Moreover, miR-200c increased the sensitivity of ovarian cancer cells to cisplatin treatment by regulating mortalin levels. Nuclear factor (NF)-κB directly regulated mortalin and miR-200b/c expression levels, while NF-κB and miR-200b/c jointly regulated the expression of mortalin. The combination of cisplatin and miR-200c significantly enhanced the therapeutic effects on ovarian cancer in vivo, suggesting that miR-200c may serve as a potential therapeutic agent for ovarian cancer. Full article
(This article belongs to the Special Issue Resistance to Therapy in Ovarian Cancers)
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Review

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20 pages, 1019 KiB  
Review
Cisplatin in Ovarian Cancer Treatment—Known Limitations in Therapy Force New Solutions
by Aleksandra Zoń and Ilona Bednarek
Int. J. Mol. Sci. 2023, 24(8), 7585; https://doi.org/10.3390/ijms24087585 - 20 Apr 2023
Cited by 19 | Viewed by 3946
Abstract
Cisplatin is one of the most commonly used anticancer drugs worldwide. It is mainly used in the treatment of ovarian cancer, but also used in testicular, bladder and lung cancers. The significant advantage of this drug is the multidirectional mechanism of its anticancer [...] Read more.
Cisplatin is one of the most commonly used anticancer drugs worldwide. It is mainly used in the treatment of ovarian cancer, but also used in testicular, bladder and lung cancers. The significant advantage of this drug is the multidirectional mechanism of its anticancer action, with the most important direction being damaging the DNA of cancer cells. Unfortunately, cisplatin displays a number of serious disadvantages, including toxicity to the most important organs, such as kidneys, heart, liver and inner ear. Moreover, a significant problem among patients with ovarian cancer, treated with cisplatin, is the development of numerous resistance mechanisms during therapy, including changes in the processes of cellular drug import and export, changes in the DNA damage repair mechanisms, as well as numerous changes in the processes of apoptosis and autophagy. Due to all of the mentioned problems, strategies to increase the effectiveness of cisplatin in the treatment of ovarian cancer are intensively sought. The most important strategy includes the development of less toxic cisplatin analogs. Another important direction is combination therapy, involving the simultaneous use of cisplatin with different anticancer drugs, substances derived from plants, temperature or radiotherapy. Many years of observations accompanying the presence of cisplatin in the therapy made it possible to provide a series of verifiable, statistically significant data, but also to show how, over time, with the new information and scientific discoveries, it is possible to describe and understand the therapeutic problems observed in practice, such as the acquisition of drug resistance by tumor cells or induction of changes in the tumor microenvironment. According to the authors, confronting what we knew so far with what new trends offer has a profound meaning. This paper presents information on the history of cisplatin and describes the molecular mechanisms of its action and the development of resistance by cancer cells. In addition, our goal was to highlight a number of therapeutic strategies to increase the effectiveness of cisplatin in the treatment of ovarian cancer, as well as to identify methods to eliminate problems associated with the use of cisplatin. Full article
(This article belongs to the Special Issue Resistance to Therapy in Ovarian Cancers)
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