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Cancers
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Translational Research in Ovarian Cancer
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Translational Research in Ovarian Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (20 May 2022) | Viewed by 12116

Special Issue Editors

Prof. Dr. Maria Flavia Di Renzo

E-Mail Website
Guest Editor
Department of Oncology, University of Torino, 10124 Torino, Italy
Interests: human ovarian cancer; patient derived models; cancer genetics; cancer genomics; tyrosine kinase targeted therapies
Special Issues, Collections and Topics in MDPI journals
Dr. Giorgio Valabrega

E-Mail Website
Co-Guest Editor
Department of Oncology, University of Torino, 10124 Torino, Italy.
Candiolo Cancer Institute, FPO-IRCCS-Candiolo, 10060 Torino, Italy
Interests: targeted therapies in ovarian cancer; resistance to PARP inhibitors; clinical trials in ovarian cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Ovarian cancer is still the most lethal gynecologic malignancy. It is diagnosed usually at advanced stages, and there has been little improvement in overall survival with standard treatment. With the exception of PARP inhibitors, targeted therapy is much less developed compared to other solid tumors and immunotherapy is under scrutiny.

This Special issue welcomes articles that illustrate and stimulate the rapid advances that are taking place in the area of ovarian cancer based on translational research. We are interested in studies on molecular mechanisms of the development and relapse of ovarian cancer, mode of action and resistance to targeted drugs, new targets for personalized therapy of the disease, and models to investigate novel therapeutic approaches transferable to clinical trials.

Prof. Maria Di Renzo
Prof. Giorgio Valabrega
Guest Editors

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 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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • mechanisms of resistance to PARP inhibitors
  • targeted therapy
  • adoptive immunotherapy
  • immune checkpoint inhibitors
  • personalized medicine in ovarian cancer

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Published Papers (4 papers)

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Editorial

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2 pages, 166 KiB  
Editorial
Translational Research in Ovarian Cancer
by Maria Flavia Di Renzo and Giorgio Valabrega
Cancers 2020, 12(12), 3676; https://doi.org/10.3390/cancers12123676 - 8 Dec 2020
Cited by 1 | Viewed by 1690
Abstract
Ovarian cancer is still the most lethal gynecologic malignancy with a median five-year survival of 48%, including the less malignant and early diagnosed cases [...] Full article
(This article belongs to the Special Issue Translational Research in Ovarian Cancer)

Research

Jump to: Editorial, Review

14 pages, 3175 KiB  
Article
Targeted Mutational Analysis of Circulating Tumor DNA to Decipher Temporal Heterogeneity of High-Grade Serous Ovarian Cancer
by Lara Paracchini, Laura Mannarino, Luca Beltrame, Fabio Landoni, Robert Fruscio, Tommaso Grassi, Maria Luisa Dalessandro, Maurizio D’Incalci and Sergio Marchini
Cancers 2022, 14(15), 3697; https://doi.org/10.3390/cancers14153697 - 29 Jul 2022
Cited by 5 | Viewed by 2206
Abstract
We have previously demonstrated that longitudinal untargeted analysis of plasma samples withdrawn from patients with high-grade serous ovarian cancer (HGS-EOC) can intercept the presence of molecular recurrence (TRm) earlier than the diagnosis of clinical recurrence (TRc). This finding opens a clinical important temporal [...] Read more.
We have previously demonstrated that longitudinal untargeted analysis of plasma samples withdrawn from patients with high-grade serous ovarian cancer (HGS-EOC) can intercept the presence of molecular recurrence (TRm) earlier than the diagnosis of clinical recurrence (TRc). This finding opens a clinical important temporal window to acquire through plasma sample analysis a real-time picture of those emerging molecular lesions that will drive and sustain the growth of relapsed disease and ultimately will confer resistance. In this proof of principle study, the same genomic libraries obtained at the diagnosis (T0), TRm and TRc were further analyzed by targeted resequencing approach to sequence the coding region of a panel of 65 genes to provide longitudinal analysis of clonal evolution as a novel strategy to support clinical decisions for the second-line treatment. Experiments were performed on plasma and tumor tissues withdrawn on a selection of previously analyzed cohorts of cases (i.e., 33 matched primary and synchronous lesions and 43 plasma samples from 18 patients). At T0, the median concordance of mutations shared by each tumor tissue biopsy and its matched plasma sample was 2.27%. This finding confirms the limit of a single tumor biopsy to be representative of the entire disease, while plasma analysis can recapitulate most of the main molecular lesions of the disease. A comparable scenario was observed during longitudinal analysis, where, with the exception of the TP53 gene and germline mutations in BRCA1/2 genes, no other gene shared the same locus specific gene mutation across T0, TRm and TRc time points. This high level of temporal heterogeneity has important implications for planning second-line treatment. For example, in three out of 13 cases, plasma ctDNA analysis at TRm or TRc reported acquired novel variants in the TP53BP1 gene not present at T0. In particular, patient 21564, potentially eligible for PARP-inhibitor (PARPi) treatment at the time of diagnosis (BRCA1 c.5182delA mutation), would unlikely respond to these drugs in second-line therapy due to the presence of eight distinct TP53BP1 variants in plasma samples collected TRc. This study demonstrates that liquid biopsy provides a real-time molecular picture to intercept those actionable genetic vulnerabilities or drug resistance mechanisms that could be used to plan a more rational second-line treatment. Full article
(This article belongs to the Special Issue Translational Research in Ovarian Cancer)
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14 pages, 1732 KiB  
Article
TCR Clonality and Genomic Instability Signatures as Prognostic Biomarkers in High Grade Serous Ovarian Cancer
by Julie Lecuelle, Romain Boidot, Hugo Mananet, Valentin Derangère, Juliette Albuisson, Vincent Goussot, Laurent Arnould, Zoé Tharin, Isabelle Ray Coquard, François Ghiringhelli, Caroline Truntzer and Jean-David Fumet
Cancers 2021, 13(17), 4394; https://doi.org/10.3390/cancers13174394 - 31 Aug 2021
Cited by 8 | Viewed by 2842
Abstract
Purpose: Immune infiltration is a prognostic factor in high-grade serous ovarian carcinoma (HGSC) but immunotherapy efficacy is disappointing. Genomic instability is now used to guide the therapeutic value of PARP inhibitors. We aimed to investigate exome-derived parameters to assess the tumor microenvironment according [...] Read more.
Purpose: Immune infiltration is a prognostic factor in high-grade serous ovarian carcinoma (HGSC) but immunotherapy efficacy is disappointing. Genomic instability is now used to guide the therapeutic value of PARP inhibitors. We aimed to investigate exome-derived parameters to assess the tumor microenvironment according to genomic instability profile. Methods: We used the HGSC TCGA (the cancer genome atlas) dataset with genomic characteristics, including homologous recombination deficiency (HRD), copy number variant (CNV) signatures, TCR (T cell receptor) clonality and abundance of tissue-infiltrating immune and stromal cell populations. We then investigated the relationship with survival data. Results: In 578 HGSC patients, HRD status, CNV signature 7 and TCR clonality were associated with longer survival. The combination of high CNV signature 7 expression and HRD status or high CNV signature 3 expression and high TCR clonality was associated with a trend towards longer survival compared to each variable alone. Combining T cell infiltrate and TCR clonality improved the prognostic value compared to T cells infiltration alone. Prognostic value of TCR clonality was confirmed in an independent cohort. Conclusions: TCR clonality is an emerging prognostic biomarker that improves T cell infiltrate information. Analysis of TCR clonality combined with genomic instability could be an interesting prognostic biomarker. Full article
(This article belongs to the Special Issue Translational Research in Ovarian Cancer)
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Review

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20 pages, 700 KiB  
Review
Inhibition of CDK4/6 as Therapeutic Approach for Ovarian Cancer Patients: Current Evidences and Future Perspectives
by Alessandra Dall’Acqua, Michele Bartoletti, Nastaran Masoudi-Khoram, Roberto Sorio, Fabio Puglisi, Barbara Belletti and Gustavo Baldassarre
Cancers 2021, 13(12), 3035; https://doi.org/10.3390/cancers13123035 - 17 Jun 2021
Cited by 19 | Viewed by 4094
Abstract
Alterations in components of the cell-cycle machinery are present in essentially all tumor types. In particular, molecular alterations resulting in dysregulation of the G1 to S phase transition have been observed in almost all human tumors, including ovarian cancer. These alterations have been [...] Read more.
Alterations in components of the cell-cycle machinery are present in essentially all tumor types. In particular, molecular alterations resulting in dysregulation of the G1 to S phase transition have been observed in almost all human tumors, including ovarian cancer. These alterations have been identified as potential therapeutic targets in several cancer types, thereby stimulating the development of small molecule inhibitors of the cyclin dependent kinases. Among these, CDK4 and CDK6 inhibitors confirmed in clinical trials that CDKs might indeed represent valid therapeutic targets in, at least some, types of cancer. CDK4 and CDK6 inhibitors are now used in clinic for the treatment of patients with estrogen receptor positive metastatic breast cancer and their clinical use is being tested in many other cancer types, alone or in combination with other agents. Here, we review the role of CDK4 and CDK6 complexes in ovarian cancer and propose the possible use of their inhibitors in the treatment of ovarian cancer patients with different types and stages of disease. Full article
(This article belongs to the Special Issue Translational Research in Ovarian Cancer)
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