Current Trends and Advances in the Diagnosis and Treatment of Gynecological Cancers

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 3442

Special Issue Editor


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Guest Editor
Department of Pathology, Oregon Health and Science University, Portland, OR 97239, USA
Interests: gynecologic; breast pathology

Special Issue Information

Dear Colleagues,

The aim of the Special Issue is to provide an update in the diagnosis and treatment of ovarian, endometrial, cervical, and vulvar cancers. Invitations are extended to experts and investigators to discuss current histological and molecular classifications of gynecologic cancers and new treatment modalities with targeted treatment options in "original" and "review" papers. The main focus is on the new biomarkers and their clinical utilities in the diagnosis and prognosis of aggressive forms of gynecologic malignancies. Investigations about the precursor lesions of cancers with their molecular results and clinical tests for early detections of gynecological tumors are the priority. Immunotherapy and immunological pathways involved in the pathogenesis of gynecological tumors will be among the discussion points. Genetically inherited cancers/familial cancer types with information from next-generation sequencing are also within the scope of the issue.

Dr. Ozlen Saglam
Guest Editor

Manuscript Submission Information

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Keywords

  • gynecological cancer
  • biomarkers
  • immunotherapy
  • genetics

Published Papers (3 papers)

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Research

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13 pages, 4288 KiB  
Article
Recurrent Somatic Copy Number Alterations and Their Association with Oncogene Expression Levels in High-Grade Ovarian Serous Carcinoma
by Hillary P. Esplen, Richard K. Yang, Awdhesh Kalia, Zhenya Tang, Guilin Tang, L. Jeffrey Medeiros and Gokce A. Toruner
Life 2023, 13(11), 2192; https://doi.org/10.3390/life13112192 - 10 Nov 2023
Cited by 1 | Viewed by 1520
Abstract
Somatic copy number alterations (SCNAs) are frequently observed in high-grade ovarian serous carcinoma (HGOSC). However, their impact on gene expression levels has not been systematically assessed. In this study, we explored the relationship between recurrent SCNA and gene expression using The Cancer Genome [...] Read more.
Somatic copy number alterations (SCNAs) are frequently observed in high-grade ovarian serous carcinoma (HGOSC). However, their impact on gene expression levels has not been systematically assessed. In this study, we explored the relationship between recurrent SCNA and gene expression using The Cancer Genome Atlas Pan Cancer dataset (OSC, TCGA, PanCancer Atlas) to identify cancer-related genes in HGOSC. We then investigated any association between highly correlated cancer genes and clinicopathological parameters, including age of diagnosis, disease stage, overall survival (OS), and progression-free survival (PFS). A total of 772 genes with recurrent SCNAs were observed. SCNA and mRNA expression levels were highly correlated for 274 genes; 24 genes were classified as a Tier 1 gene in the Cancer Gene Census in the Catalogue of Somatic Mutations in Cancer (CGC-COSMIC). Of these, 11 Tier 1 genes had highly correlated SCNA and mRNA expression levels: TBL1XR1, PIK3CA, UBR5, EIF3E, RAD21, EXT1, RECQL4, KRAS, PRKACA, BRD4, and TPM4. There was no association between gene amplification and disease stage or PFS. EIF3E, RAD21, and EXT1 were more frequently amplified in younger patients, specifically those under the age of 55 years. Patients with tumors carrying PRKACA, BRD4, or TPM4 amplification were associated with a significantly shorter OS. RECQL4 amplification was more frequent in younger patients, and tumors with this amplification were associated with a significantly better OS. Full article
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Review

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15 pages, 1361 KiB  
Review
Genetic Links between Endometriosis and Endometriosis-Associated Ovarian Cancer—A Narrative Review (Endometriosis-Associated Cancer)
by Tanja Pejovic, Ann M. Cathcart, Rofieda Alwaqfi, Marjorie N. Brooks, Rachel Kelsall and Farr R. Nezhat
Life 2024, 14(6), 704; https://doi.org/10.3390/life14060704 - 30 May 2024
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Abstract
Endometriosis is a frequent, estrogen-dependent, chronic disease, characterized by the presence of endometrial glands and stroma outside of the uterine cavity. Although it is not considered a precursor of cancer, endometriosis is associated with ovarian cancer. In this review, we summarized the evidence [...] Read more.
Endometriosis is a frequent, estrogen-dependent, chronic disease, characterized by the presence of endometrial glands and stroma outside of the uterine cavity. Although it is not considered a precursor of cancer, endometriosis is associated with ovarian cancer. In this review, we summarized the evidence that clear-cell and endometrioid ovarian carcinomas (endometriosis-associated ovarian carcinoma—EAOC) may arise in endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interaction domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in phosphatidylinositol 3-kinase (PI3K) which frequently coexist. Recent studies have also suggested the simultaneous role of the PTEN tumor-suppressor gene in the early malignant transformation of endometriosis and the contribution of deficient MMR (mismatch repair) protein status in the pathogenesis of EAOC. In addition to activating and inactivating mutations in cancer driver genes, the complex pathogenesis of EAOC involves multiple other mechanisms such as the modulation of cancer driver genes via the transcriptional and post-translational (miRNA) modulation of cancer driver genes and the interplay with the inflammatory tissue microenvironment. This knowledge is being translated into the clinical management of endometriosis and EAOC. This includes the identification of the new biomarkers predictive of the risk of endometriosis and cancer, and it will shape the precision oncology treatment of EAOC. Full article
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14 pages, 8817 KiB  
Review
Harnessing γδ T Cells against Human Gynecologic Cancers
by Jose R. Conejo-Garcia, Carmen M. Anadon, Luis U. Lopez-Bailon and Ricardo A. Chaurio
Life 2024, 14(3), 325; https://doi.org/10.3390/life14030325 - 29 Feb 2024
Viewed by 1288
Abstract
Immuno-oncology has traditionally focused on conventional MHC-restricted αβ T cells. Yet, unconventional γδ T cells, which kill tumor cells in an MHC-unrestricted manner, display characteristics of effector activity and stemness without exhaustion and are nearly universally observed in human gynecologic malignancies, correlating with [...] Read more.
Immuno-oncology has traditionally focused on conventional MHC-restricted αβ T cells. Yet, unconventional γδ T cells, which kill tumor cells in an MHC-unrestricted manner, display characteristics of effector activity and stemness without exhaustion and are nearly universally observed in human gynecologic malignancies, correlating with improved outcomes. These cells do not have a clear counterpart in mice but are also found in the healthy female reproductive tract. Interventions that modulate their in vivo activity, or cellular therapies utilizing γδ T cells as an allogeneic, “off-the-shelf” platform (e.g., for chimeric antigen receptor expression) hold significant potential against challenging tumors like ovarian cancer, which has been stubbornly resistant to the immune checkpoint inhibitors that change the landscape of other human tumors. Here, we discuss recent discoveries on the specific populations of γδ T cells that infiltrate human gynecologic cancers, their anti-tumor activity, and the prospect of redirecting their effector function against tumor cells to develop a new generation of immunotherapies that extends beyond the traditional αβ T cell-centric view of the field. Full article
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