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Cancers
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High Risk Gynecological Cancers
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High Risk Gynecological Cancers

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (1 October 2021) | Viewed by 30893

Special Issue Editors

Dr. Suzy Marie E. Scholl

E-Mail Website
Guest Editor
Department of drug development and innovation, Institut Curie, Paris, France
Interests: Gynaecological cancer and specifically cervical cancer; molecular and pharmacological profiling in tumours; cell lines; single cells; in-silico models; biomarker research; personalized medicine treatment
Dr. Eva Colas

E-Mail Website
Guest Editor
Group of Biomedical Research in Gynecology, Vall Hebron Institute of Research, Barcelona, Spain
Interests: endometrial cancer; endometriosis; biomarker research; personalized medicine; treatment

Special Issue Information

Dear Colleagues,

This Special Issue of Cancers calls for contributions from the translational research field with a focus on cancers that initiate in the female genital tract and that resist standard therapies. Cancers of the uterine cervix, the endometrium, or the ovary have a total incidence of 1.2 Million per year worldwide and a major impact on mortality in women of all age categories.

Presently, targeted therapies only benefit a minority of patients diagnosed with a high-risk gynecological cancer. To address the complexity of multiple genetic alterations in individual cancers, there is a need to deepen our understanding of individual tumor heterogeneity and to develop a methodology for applying combinations of therapies to the clinic. Precision oncology is likely to enable targeted therapies in association with classical chemotherapies. This can be modeled based on response prediction or inferred from preclinical work and in silico modeling. Precision oncology equally requires a new clinical trial methodology that is scientifically valid as well as acceptable to patients.

We aim to present innovative scientific contributions on molecular and pharmacological profiling in tumors, cell lines, single cells, PDX models, and in silico models. Scientific work should inform us about: 1) molecular alterations that depict the complexity of high-risk gynecological cancers; 2) the discovery of novel drugs and/or drug combinations that are effective for specific molecular profiles (constellations) associated with a poor outcome; and 3) the identification of diagnostic, predictive, and treatment-response biomarkers.

For this Special Issue, we welcome manuscripts that provide translational information on the topics mentioned above, with a focus on high-risk cervical, endometrial, and ovarian cancers. We will also consider manuscripts that provide translational information on other gynecological cancer types with a lesser incidence.

Dr. Suzy Marie E. Scholl
Dr. Eva Colas
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

  • gynecological cáncer
  • high-risk cáncer
  • endometrial cáncer
  • cervical cáncer
  • ovarian cáncer
  • personalized treatment
  • diagnostic and predictive biomarkers
  • translational research
  • bio-informatics
  • big data
  • molecular and pharmacological profiling
  • tumor models: cell lines and single cells
  • PDX models
  • In silico models

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Published Papers (8 papers)

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Research

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15 pages, 1934 KiB  
Article
In silico Approach for Validating and Unveiling New Applications for Prognostic Biomarkers of Endometrial Cancer
by Eva Coll-de la Rubia, Elena Martinez-Garcia, Gunnar Dittmar, Petr V. Nazarov, Vicente Bebia, Silvia Cabrera, Antonio Gil-Moreno and Eva Colás
Cancers 2021, 13(20), 5052; https://doi.org/10.3390/cancers13205052 - 9 Oct 2021
Cited by 7 | Viewed by 2925
Abstract
Endometrial cancer (EC) mortality is directly associated with the presence of prognostic factors. Current stratification systems are not accurate enough to predict the outcome of patients. Therefore, identifying more accurate prognostic EC biomarkers is crucial. We aimed to validate 255 prognostic biomarkers identified [...] Read more.
Endometrial cancer (EC) mortality is directly associated with the presence of prognostic factors. Current stratification systems are not accurate enough to predict the outcome of patients. Therefore, identifying more accurate prognostic EC biomarkers is crucial. We aimed to validate 255 prognostic biomarkers identified in multiple studies and explore their prognostic application by analyzing them in TCGA and CPTAC datasets. We analyzed the mRNA and proteomic expression data to assess the statistical prognostic performance of the 255 proteins. Significant biomarkers related to overall survival (OS) and recurrence-free survival (RFS) were combined and signatures generated. A total of 30 biomarkers were associated either to one or more of the following prognostic factors: histological type (n = 15), histological grade (n = 6), FIGO stage (n = 1), molecular classification (n = 16), or they were associated to OS (n = 11), and RFS (n = 5). A prognostic signature composed of 11 proteins increased the accuracy to predict OS (AUC = 0.827). The study validates and identifies new potential applications of 30 proteins as prognostic biomarkers and suggests to further study under-studied biomarkers such as TPX2, and confirms already used biomarkers such as MSH6, MSH2, or L1CAM. These results are expected to advance the quest for biomarkers to accurately assess the risk of EC patients. Full article
(This article belongs to the Special Issue High Risk Gynecological Cancers)
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24 pages, 5639 KiB  
Article
The Stress-Inducible BCL2A1 Is Required for Ovarian Cancer Metastatic Progression in the Peritoneal Microenvironment
by Rui Liang, Mingo M. H. Yung, Fangfang He, Peili Jiao, Karen K. L. Chan, Hextan Y. S. Ngan and David W. Chan
Cancers 2021, 13(18), 4577; https://doi.org/10.3390/cancers13184577 - 12 Sep 2021
Cited by 7 | Viewed by 2799
Abstract
Emerging evidence indicates that hypoxia plays a critical role in governing the transcoelomic metastasis of ovarian cancer. Hence, targeting hypoxia may be a promising approach to prevent the metastasis of ovarian cancer. Here, we report that BCL2A1, a BCL2 family member, acts as [...] Read more.
Emerging evidence indicates that hypoxia plays a critical role in governing the transcoelomic metastasis of ovarian cancer. Hence, targeting hypoxia may be a promising approach to prevent the metastasis of ovarian cancer. Here, we report that BCL2A1, a BCL2 family member, acts as a hypoxia-inducible gene for promoting tumor progression in ovarian cancer peritoneal metastases. We demonstrated that BCL2A1 was induced not only by hypoxia but also other physiological stresses through NF-κB signaling and then was gradually reduced by the ubiquitin-proteasome pathway in ascites-derived ovarian cancer cells. The upregulated BCL2A1 was frequently found in advanced metastatic ovarian cancer cells, suggesting its clinical relevance in ovarian cancer metastatic progression. Functionally, BCL2A1 enhanced the foci formation ability of ovarian cancer cells in a stress-conditioned medium, colony formation in an ex vivo omental tumor model, and tumor dissemination in vivo. Under stress conditions, BCL2A1 accumulated and colocalized with mitochondria to suppress intrinsic cell apoptosis by interacting with the BH3-only subfamily BCL2 members HRK/BAD/BID in ovarian cancer cells. These findings indicate that BCL2A1 is an early response factor that maintains the survival of ovarian cancer cells in the harsh tumor microenvironment. Full article
(This article belongs to the Special Issue High Risk Gynecological Cancers)
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12 pages, 2563 KiB  
Article
The Prognostic Role of LRIG Proteins in Endometrial Cancer
by Zoia Razumova, Husam Oda, Igor Govorov, Eva Lundin, Ellinor Östensson, David Lindquist and Miriam Mints
Cancers 2021, 13(6), 1361; https://doi.org/10.3390/cancers13061361 - 17 Mar 2021
Cited by 1 | Viewed by 2520
Abstract
Endometrial cancer (EC) is the most common gynecologic malignancy in Sweden and it has various prognostic factors. The LRIG family is a group of three integral surface proteins with a similar domain organization. The study aimed to explore LRIG family as prognostic factor [...] Read more.
Endometrial cancer (EC) is the most common gynecologic malignancy in Sweden and it has various prognostic factors. The LRIG family is a group of three integral surface proteins with a similar domain organization. The study aimed to explore LRIG family as prognostic factor proteins in EC. The initial study cohort included 100 women with EC who were treated at the Department of Women’s and Children’s Health, Karolinska University Hospital Solna, between 2007 and 2012. We assessed the associations between LRIG protein expression and type, grade, and stage of EC, as well as progression-free and overall survival. Immunohistochemistry results revealed that most women in the analytical sample had >50% LRIG1-, LRIG2- and LRIG3-positive cells. A statistically significant association was observed between having a high number of LRIG3-positive cells and superior overall survival (incidence rate ratio = 0.977; 95% confidence interval: 0.958–0.996, p = 0.019). Moreover, positive LRIG3 staining of the cell membrane was associated with reducing in the risk of death (hazard ratio = 0.23; 95% confidence interval: 0.09–0.57). Our results show that LRIG3 expression might be a prognostic factor in EC. The role of LRIG1 and LRIG2 expression remains to be further investigated. Full article
(This article belongs to the Special Issue High Risk Gynecological Cancers)
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9 pages, 641 KiB  
Article
Molecular Characterization of Ovarian Yolk Sac Tumor (OYST)
by Khalil Hodroj, Aleksandra Stevovic, Valery Attignon, Domenico Ferraioli, Pierre Meeus, Sabrina Croce, Nicolas Chopin, Lea Rossi, Anne Floquet, Christine Rousset-Jablonski, Olivier Tredan, Frédéric Guyon, Isabelle Treilleux, Corinne Rannou, Marie Morfouace and Isabelle Ray-Coquard
Cancers 2021, 13(2), 220; https://doi.org/10.3390/cancers13020220 - 9 Jan 2021
Cited by 8 | Viewed by 2834
Abstract
Most patients with malignant ovarian germ cell tumors (MOGTCs) have a very good prognosis and chemotherapy provides curative treatment; however, patients with yolk sac tumors (OYSTs) have a significantly worse prognosis. OYSTs are rare tumors and promising results are expected with the use [...] Read more.
Most patients with malignant ovarian germ cell tumors (MOGTCs) have a very good prognosis and chemotherapy provides curative treatment; however, patients with yolk sac tumors (OYSTs) have a significantly worse prognosis. OYSTs are rare tumors and promising results are expected with the use of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens. We initiated a project in collaboration with EORTC SPECTA, to explore the molecular characteristics of OYSTs. The pilot project used retrospective samples from ten OYST relapsed and disease-free patients. Each patient had a molecular analysis performed with FoundationOne CDx describing the following variables according to the Foundation Medicine Incorporation (FMI): alteration type (SNV, deletion), actionable gene alteration, therapies approved in EU (for patient’s tumor type and other tumor types), tumor mutational burden (TMB), and microsatellite instability (MSI) status. A total of 10 patients with OYST diagnosed between 2007 and 2017 had a molecular analysis. A molecular alteration was identified in four patients (40%). A subset of three patients (33.3% of all patients) harbored targetable oncogenic mutations in KRAS, KIT, ARID1A. Two patients at relapse harbored a targetable mutation. This retrospective study identifies clinically relevant molecular alterations for all relapsed patients with molecular analysis. Dedicated studies are needed to demonstrate the efficacy of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens and to explore the potential relationship of a molecular alteration and patient outcome. Full article
(This article belongs to the Special Issue High Risk Gynecological Cancers)
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Review

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23 pages, 1018 KiB  
Review
New Trends in the Detection of Gynecological Precancerous Lesions and Early-Stage Cancers
by Jitka Holcakova, Martin Bartosik, Milan Anton, Lubos Minar, Jitka Hausnerova, Marketa Bednarikova, Vit Weinberger and Roman Hrstka
Cancers 2021, 13(24), 6339; https://doi.org/10.3390/cancers13246339 - 17 Dec 2021
Cited by 14 | Viewed by 4205
Abstract
The prevention and early diagnostics of precancerous stages are key aspects of contemporary oncology. In cervical cancer, well-organized screening and vaccination programs, especially in developed countries, are responsible for the dramatic decline of invasive cancer incidence and mortality. Cytological screening has a long [...] Read more.
The prevention and early diagnostics of precancerous stages are key aspects of contemporary oncology. In cervical cancer, well-organized screening and vaccination programs, especially in developed countries, are responsible for the dramatic decline of invasive cancer incidence and mortality. Cytological screening has a long and successful history, and the ongoing implementation of HPV triage with increased sensitivity can further decrease mortality. On the other hand, endometrial and ovarian cancers are characterized by a poor accessibility to specimen collection, which represents a major complication for early diagnostics. Therefore, despite relatively promising data from evaluating the combined effects of genetic variants, population screening does not exist, and the implementation of new biomarkers is, thus, necessary. The introduction of various circulating biomarkers is of potential interest due to the considerable heterogeneity of cancer, as highlighted in this review, which focuses exclusively on the most common tumors of the genital tract, namely, cervical, endometrial, and ovarian cancers. However, it is clearly shown that these malignancies represent different entities that evolve in different ways, and it is therefore necessary to use different methods for their diagnosis and treatment. Full article
(This article belongs to the Special Issue High Risk Gynecological Cancers)
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17 pages, 986 KiB  
Review
Endometrial Cancer Molecular Characterization: The Key to Identifying High-Risk Patients and Defining Guidelines for Clinical Decision-Making?
by Regina Esi Mensimah Baiden-Amissah, Daniela Annibali, Sandra Tuyaerts and Frederic Amant
Cancers 2021, 13(16), 3988; https://doi.org/10.3390/cancers13163988 - 7 Aug 2021
Cited by 15 | Viewed by 5672
Abstract
Endometrial carcinomas (EC) are the sixth most common cancer in women worldwide and the most prevalent in the developed world. ECs have been historically sub-classified in two major groups, type I and type II, based primarily on histopathological characteristics. Notwithstanding the usefulness of [...] Read more.
Endometrial carcinomas (EC) are the sixth most common cancer in women worldwide and the most prevalent in the developed world. ECs have been historically sub-classified in two major groups, type I and type II, based primarily on histopathological characteristics. Notwithstanding the usefulness of such classification in the clinics, until now it failed to adequately stratify patients preoperatively into low- or high-risk groups. Pieces of evidence point to the fact that molecular features could also serve as a base for better patients’ risk stratification and treatment decision-making. The Cancer Genome Atlas (TCGA), back in 2013, redefined EC into four main molecular subgroups. Despite the high hopes that welcomed the possibility to incorporate molecular features into practice, currently they have not been systematically applied in the clinics. Here, we outline how the emerging molecular patterns can be used as prognostic factors together with tumor histopathology and grade, and how they can help to identify high-risk EC subpopulations for better risk stratification and treatment strategy improvement. Considering the importance of the use of preclinical models in translational research, we also discuss how the new patient-derived models can help in identifying novel potential targets and help in treatment decisions. Full article
(This article belongs to the Special Issue High Risk Gynecological Cancers)
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17 pages, 542 KiB  
Review
Future Screening Prospects for Ovarian Cancer
by Diana Žilovič, Rūta Čiurlienė, Rasa Sabaliauskaitė and Sonata Jarmalaitė
Cancers 2021, 13(15), 3840; https://doi.org/10.3390/cancers13153840 - 30 Jul 2021
Cited by 26 | Viewed by 5038
Abstract
Current diagnostic tools used in clinical practice such as transvaginal ultrasound, CA 125, and HE4 are not sensitive and specific enough to diagnose OC in the early stages. A lack of early symptoms and an effective asymptomatic population screening strategy leads to a [...] Read more.
Current diagnostic tools used in clinical practice such as transvaginal ultrasound, CA 125, and HE4 are not sensitive and specific enough to diagnose OC in the early stages. A lack of early symptoms and an effective asymptomatic population screening strategy leads to a poor prognosis in OC. New diagnostic and screening methods are urgently needed for early OC diagnosis. Liquid biopsies have been considered as a new noninvasive and promising method, using plasma/serum, uterine lavage, and urine samples for early cancer detection. We analyzed recent studies on molecular biomarkers with specific emphasis on liquid biopsy methods and diagnostic efficacy for OC through the detection of circulating tumor cells, circulating cell-free DNA, small noncoding RNAs, and tumor-educated platelets. Full article
(This article belongs to the Special Issue High Risk Gynecological Cancers)
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15 pages, 5997 KiB  
Review
Resistance to Immune Checkpoint Blockade in Uterine Leiomyosarcoma: What Can We Learn from Other Cancer Types?
by Wout De Wispelaere, Daniela Annibali, Sandra Tuyaerts, Diether Lambrechts and Frédéric Amant
Cancers 2021, 13(9), 2040; https://doi.org/10.3390/cancers13092040 - 23 Apr 2021
Cited by 5 | Viewed by 3532
Abstract
The onset of immune checkpoint blockade (ICB) therapy over the last decade has transformed the therapeutic landscape in oncology. ICB has shown unprecedented clinical activity and durable responses in a variety of difficult-to-treat cancers. However, despite these promising long-term responses, a majority of [...] Read more.
The onset of immune checkpoint blockade (ICB) therapy over the last decade has transformed the therapeutic landscape in oncology. ICB has shown unprecedented clinical activity and durable responses in a variety of difficult-to-treat cancers. However, despite these promising long-term responses, a majority of patients fail to respond to single-agent therapy, demonstrating primary or acquired resistance. Uterine leiomyosarcoma (uLMS) is a rare high-risk gynecological cancer with very limited treatment options. Despite research indicating a strong potential for ICB in uLMS, a clinical trial assessing the response to immunotherapy with single-agent nivolumab in advanced-stage uLMS showed no clinical benefit. Many mechanisms of resistance to ICB have been characterized in a variety of tumor types, and many more continue to be uncovered. However, the mechanisms of resistance to ICB in uLMS remain largely unexplored. By elucidating and targeting mechanisms of resistance, treatments can be tailored to improve clinical outcomes. Therefore, in this review we will explore what is known about the immunosuppressive microenvironment of uLMS, link these data to possible resistance mechanisms extrapolated from other cancer types, and discuss potential therapeutic strategies to overcome resistance. Full article
(This article belongs to the Special Issue High Risk Gynecological Cancers)
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