Personalized Medicine in Gynecological Cancer

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 6684

Special Issue Editors

1. Laboratorio de Microbiología Celular, Instituto de Investigación e Innovación en Salud, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago, Chile
2. Centro de Estudios Avanzados en Enfermedades Crónicas (ACCDiS), Independencia, Santiago 8380000, Chile
Interests: molecular biology; gastric cancer; ovarian cancer; molecular pathogenesis; bacterial infections; translational control; natural compounds
Hospital Clínico Universidad de Chile, Departamento de Obstetricia y Ginecología, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile
Interests: ovarian cancer; repurposing drugs; ovarian cancer treatments; new cancer markers; gynecological oncology; reproductive endocrinology
Departamento de Obstetricia y Ginecología, Facultad de Medicina, Hospital Clínico Universidad de Chile, Universidad de Chile, Santiago 8380453, Chile
Interests: ovarian cancer; neurotrophins; angiogenesis; microRNAs for cancer treatment; ovarian cancer pathogenesis; neuroendocrine regulation of ovary
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Special Issue Information

Dear Colleagues,

Gynecological cancer are a set of neoplasm that include ovarian cancer, cervical cancer and endometrial cancer as the most common pathologies. They represent a severe threat to women’s health, since their high incidence, high mortality, limited therapeutic late efficacy, recurrence, and the emergence of drug resistance. In general, the gynecological cancer diagnosis is mainly based on histopathological scoring with limited therapeutic options. In this context, the progress in personalized medicine, also known as “precision medicine” is vital to individualizing cancer care by treating tumors based on genetic and transcriptional patterns. To date, this notion has gone beyond nucleic acid signatures; thus, additional omic approaches (Big data) such as Proteomic, Metabolomic and Epigenetic have been developed to create novel targeted therapies for most cancer types. For instance, despite complete remission usually being reached in ovarian cancer, most tumors will recur within two years, and the rapid apparition of resistance to chemotherapy is observed. Thus, remission-maintenance regimens have included most personalized strategies and alternative therapies to overcome the problem of resistance and increase the survival of patients, including the use of anti-angiogenic molecules (Bevacizumab), PARP inhibitors, and directed immunotherapies. This point is even worse considering the genomic heterogeneity observed during the transition from the primary tumor to recurrence and metastasis.

The complexity and heterogeneity of gynecological cancer represent a tremendous opportunity for the development of personalized medicine; also, considering a most productive cross-talk between basic research and clinical application and the limitations imposed by particular regional situations in terms of technologic capacities and resources.

The journal Pharmaceuticals invites original articles and reviews to shed light on the challenges, opportunities, and current personalized therapies for the special issue “Personalized Medicine in Gynecological Cancer” of the journal. Topics include insight into the genetic characterization of gynecological cancers, new biomarkers for improving diagnosis and treatment, and new therapeutic approaches with a focus on targeted therapy.

Dr. Manuel Valenzuela-Valderrama
Dr. Maritza P. Garrido Palma
Prof. Dr. Carmen Aurora Romero
Guest Editors

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Keywords

  • gynecological cancer
  • personalized medicine
  • ovarian cancer
  • chemoresistance
  • endometrial cancer
  • cervical cancer
  • OMICs
  • personalized drug therapy
  • biomarkers

Published Papers (4 papers)

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Research

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18 pages, 2521 KiB  
Article
Characteristics of Extracellular Vesicles from a High-Grade Serous Ovarian Cancer Cell Line Derived from a Platinum-Resistant Patient as a Potential Tool for Aiding the Prediction of Responses to Chemotherapy
by Katarina Černe, Nuša Kelhar, Nataša Resnik, Maruša Herzog, Lana Vodnik, Peter Veranič and Borut Kobal
Pharmaceuticals 2023, 16(6), 907; https://doi.org/10.3390/ph16060907 - 20 Jun 2023
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Abstract
Platinum-resistant high-grade serous ovarian cancer (HGSOC) is invariably a fatal disease. A central goal of ovarian cancer research is therefore to develop new strategies to overcome platinum resistance. Treatment is thus moving towards personalized therapy. However, validated molecular biomarkers that predict patients’ risk [...] Read more.
Platinum-resistant high-grade serous ovarian cancer (HGSOC) is invariably a fatal disease. A central goal of ovarian cancer research is therefore to develop new strategies to overcome platinum resistance. Treatment is thus moving towards personalized therapy. However, validated molecular biomarkers that predict patients’ risk of developing platinum resistance are still lacking. Extracellular vesicles (EVs) are promising candidate biomarkers. EpCAM-specific EVs are largely unexplored biomarkers for predicting chemoresistance. Using transmission electron microscopy, nanoparticle tracking analysis and flow cytometry, we compared the characteristics of EVs released from a cell line derived from a clinically confirmed cisplatin-resistant patient (OAW28) and EVs released from two cell lines from tumors sensitive to platinum-based chemotherapy (PEO1 and OAW42). We demonstrated that EVs released from the HGSOC cell line of chemoresistant patients exhibited greater size heterogeneity, a larger proportion of medium/large (>200 nm) Evs and a higher number of released EpCAM-positive EVs of different sizes, although the expression of EpCAM was predominant in EVs larger than 400 nm. We also found a strong positive correlation between the concentration of EpCAM-positive EVs and the expression of cellular EpCAM. These results may contribute to the prediction of platinum resistance in the future, although they should first be validated in clinical samples. Full article
(This article belongs to the Special Issue Personalized Medicine in Gynecological Cancer)
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12 pages, 898 KiB  
Article
Potential Targeted Therapies in Ovarian Cancer
by Yagmur Sisman, Lau Kræsing Vestergaard, Douglas Nogueira Perez de Oliveira, Tim Svenstrup Poulsen, Tine Henrichsen Schnack, Claus Høgdall and Estrid Høgdall
Pharmaceuticals 2022, 15(11), 1324; https://doi.org/10.3390/ph15111324 - 26 Oct 2022
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Abstract
Background: We aimed to identify somatic pathogenic and likely pathogenic mutations using next-generation sequencing (NGS). The mutational findings were held against clinically well-described data to identify potential targeted therapies in Danish patients diagnosed with high-grade serous ovarian cancer (HGSC). Methods: We characterized the [...] Read more.
Background: We aimed to identify somatic pathogenic and likely pathogenic mutations using next-generation sequencing (NGS). The mutational findings were held against clinically well-described data to identify potential targeted therapies in Danish patients diagnosed with high-grade serous ovarian cancer (HGSC). Methods: We characterized the mutational profile of 128 HGSC patients. Clinical data were obtained from the Danish Gynecological Database and tissue samples were collected through the Danish CancerBiobank. DNA was analyzed using NGS. Results: 47 (37%) patients were platinum-sensitive, 32 (25%) partially platinum-sensitive, 35 (27%) platinum-resistant, and three (2%) platinum-refractory, while 11 (9%) patients did not receive chemotherapy. Overall, 27 (21%) had known druggable targets. Twelve (26%) platinum-sensitive patients had druggable targets for PARP inhibitors: one for tyrosine kinase inhibitors and one for immunotherapy treatment. Eight (25%) partially platinum-sensitive patients had druggable targets: seven were eligible for PARP inhibitors and one was potentially eligible for alpesilib and hormone therapy. Seven (20%) platinum-resistant patients had druggable targets: six (86%) were potentially eligible for PARP inhibitors, one for immunotherapy, and one for erdafitinib. Conclusions: PARP inhibitors are the most frequent potential targeted therapy in HGSC. However, other targeted therapies remain relevant for investigation according to our mutational findings. Full article
(This article belongs to the Special Issue Personalized Medicine in Gynecological Cancer)
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Review

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19 pages, 1073 KiB  
Review
Mechanisms of Regulation of the Expression of miRNAs and lncRNAs by Metformin in Ovarian Cancer
by Ignacio Alfaro, Margarita Vega, Carmen Romero and Maritza P. Garrido
Pharmaceuticals 2023, 16(11), 1515; https://doi.org/10.3390/ph16111515 - 24 Oct 2023
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Abstract
Ovarian cancer (OC) is one of the most lethal gynecological malignancies. The use of biological compounds such as non-coding RNAs (ncRNAs) is being considered as a therapeutic option to improve or complement current treatments since the deregulation of ncRNAs has been implicated in [...] Read more.
Ovarian cancer (OC) is one of the most lethal gynecological malignancies. The use of biological compounds such as non-coding RNAs (ncRNAs) is being considered as a therapeutic option to improve or complement current treatments since the deregulation of ncRNAs has been implicated in the pathogenesis and progression of OC. Old drugs with antitumoral properties have also been studied in the context of cancer, although their antitumor mechanisms are not fully clear. For instance, the antidiabetic drug metformin has shown pleiotropic effects in several in vitro models of cancer, including OC. Interestingly, metformin has been reported to regulate ncRNAs, which could explain its diverse effects on tumor cells. In this review, we discuss the mechanism of epigenetic regulation described for metformin, with a focus on the evidence of metformin-dependent microRNA (miRNAs) and long non-coding RNA (lncRNAs) regulation in OC. Full article
(This article belongs to the Special Issue Personalized Medicine in Gynecological Cancer)
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21 pages, 1288 KiB  
Review
Ion Channels and Personalized Medicine in Gynecological Cancers
by Ana Ramírez, Ingrid Ogonaga-Borja, Brenda Acosta, Andrea Jazmín Chiliquinga, Jaime de la Garza, Patricio Gariglio, Rodolfo Ocádiz-Delgado, Cecilia Bañuelos and Javier Camacho
Pharmaceuticals 2023, 16(6), 800; https://doi.org/10.3390/ph16060800 - 29 May 2023
Viewed by 1890
Abstract
Targeted therapy against cancer plays a key role in delivering safer and more efficient treatments. In the last decades, ion channels have been studied for their participation in oncogenic processes because their aberrant expression and/or function have been associated with different types of [...] Read more.
Targeted therapy against cancer plays a key role in delivering safer and more efficient treatments. In the last decades, ion channels have been studied for their participation in oncogenic processes because their aberrant expression and/or function have been associated with different types of malignancies, including ovarian, cervical, and endometrial cancer. The altered expression or function of several ion channels have been associated with tumor aggressiveness, increased proliferation, migration, invasion, and metastasis of cancer cells and with poor prognosis in gynecological cancer patients. Most ion channels are integral membrane proteins easily accessible by drugs. Interestingly, a plethora of ion channel blockers have demonstrated anticancer activity. Consequently, some ion channels have been proposed as oncogenes, cancer, and prognostic biomarkers, as well as therapeutic targets in gynecological cancers. Here, we review the association of ion channels with the properties of cancer cells in these tumors, which makes them very promising candidates to be exploited in personalized medicine. The detailed analysis of the expression pattern and function of ion channels could help to improve the clinical outcomes in gynecological cancer patients. Full article
(This article belongs to the Special Issue Personalized Medicine in Gynecological Cancer)
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