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  1. Article: Is there a role for immunotherapy in ovarian cancer?

    Giannone, Gaia / Valabrega, Giorgio

    Annals of translational medicine

    2020  Volume 7, Issue Suppl 8, Page(s) S276

    Language English
    Publishing date 2020-01-03
    Publishing country China
    Document type Editorial ; Comment
    ZDB-ID 2893931-1
    ISSN 2305-5847 ; 2305-5839
    ISSN (online) 2305-5847
    ISSN 2305-5839
    DOI 10.21037/atm.2019.12.13
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Searching for prognostic markers for Stage I epithelial ovarian cancer: A role for systemic inflammatory markers.

    Borella, Fulvio / Bertero, Luca / Valabrega, Giorgio / Fucina, Stefano / Cassoni, Paola / Benedetto, Chiara

    International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics

    2023  Volume 164, Issue 1, Page(s) 262–269

    Abstract: Objective: To determine the prognostic role of systemic inflammatory markers for Stage I epithelial ovarian cancer (EOC).: Materials and methods: We performed a retrospective, single-center, observational study. We included patients with Stage I EOC ... ...

    Abstract Objective: To determine the prognostic role of systemic inflammatory markers for Stage I epithelial ovarian cancer (EOC).
    Materials and methods: We performed a retrospective, single-center, observational study. We included patients with Stage I EOC cancer undergoing primary surgery between 1993 and 2016. Inflammatory markers were assessed by analyzing blood samples collected at initial diagnosis before EOC surgery. We evaluated these markers' association with disease-free survival (DFS) and cancer-specific survival (CSS).
    Results: We included 176 women in our study. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) were related to both DFS and CSS in the univariate analysis. In the multivariate Cox analysis, adjuvant chemotherapy (hazard ratio [HR] 0.17, 95% confidence interval [CI] 0.04-0.71, P = 0.02) and SII ≥730 (HR 6.84, 95% CI 1.30-35.9, P = 0.023) were independent predictors of DFS, while FIGO Stage IB-IC (HR 7.91, 95% CI 1.04-59.8, P = 0.04), NLR ≥3 (HR 56.8, 95% CI 7.46-433, P < 0.001) and PLR ≥169 (HR 49.1 95% CI 11.1-217.8, P = 0.005) were independent predictors of CSS.
    Conclusions: Systemic inflammatory markers are easily obtainable from patients' routine blood analyses and may represent inexpensive and reproducible prognostic markers in early-stage EOC.
    MeSH term(s) Humans ; Female ; Prognosis ; Carcinoma, Ovarian Epithelial/diagnosis ; Retrospective Studies ; Lymphocytes ; Inflammation ; Neutrophils ; Ovarian Neoplasms
    Language English
    Publishing date 2023-07-27
    Publishing country United States
    Document type Observational Study ; Journal Article
    ZDB-ID 80149-5
    ISSN 1879-3479 ; 0020-7292
    ISSN (online) 1879-3479
    ISSN 0020-7292
    DOI 10.1002/ijgo.15014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: The Role of PARP Inhibitors in the Ovarian Cancer Microenvironment: Moving Forward From Synthetic Lethality.

    Turinetto, Margherita / Scotto, Giulia / Tuninetti, Valentina / Giannone, Gaia / Valabrega, Giorgio

    Frontiers in oncology

    2021  Volume 11, Page(s) 689829

    Abstract: PARP inhibitors (PARPi) have shown promising clinical results and have revolutionized the landscape of ovarian cancer management in the last few years. While the core mechanism of action of these drugs has been largely analyzed, the interaction between ... ...

    Abstract PARP inhibitors (PARPi) have shown promising clinical results and have revolutionized the landscape of ovarian cancer management in the last few years. While the core mechanism of action of these drugs has been largely analyzed, the interaction between PARP inhibitors and the microenvironment has been scarcely researched so far. Recent data shows a variety of mechanism through which PARPi might influence the tumor microenvironment and especially the immune system response, that might even partly be the reason behind PARPi efficacy. One of many pathways that are affected is the cGAS-cGAMP-STING; the upregulation of STING (stimulator of interferon genes), produces more Interferon ϒ and pro inflammatory cytokines, thus increasing intratumoral CD4+ and CD8+ T cells. Upregulation of immune checkpoints such as PD1-PDL1 has also been observed. Another interesting mechanism of interaction between PARPi and microenvironment is the ability of PARPi to kill hypoxic cells, as these cells show an intrinsic reduction in the expression and function of the proteins involved in HR. This process has been defined "contextual synthetic lethality". Despite ovarian cancer having always been considered a poor responder to immune therapy, data is now shedding a new light on the matter. First, OC is much more heterogenous than previously thought, therefore it is fundamental to select predictive biomarkers for target therapies. While single agent therapies have not yielded significant results on the long term, influencing the immune system and the tumor microenvironment
    Language English
    Publishing date 2021-06-14
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2021.689829
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Clinical Implications of DNA Repair Defects in High-Grade Serous Ovarian Carcinomas.

    Milanesio, Michela Camilla / Giordano, Silvia / Valabrega, Giorgio

    Cancers

    2020  Volume 12, Issue 5

    Abstract: Despite significant improvements in surgical and medical management, high grade serous ovarian cancer (HGSOC) still represents the deadliest gynecologic malignancy and the fifth most frequent cause of cancer-related mortality in women in the USA. Since ... ...

    Abstract Despite significant improvements in surgical and medical management, high grade serous ovarian cancer (HGSOC) still represents the deadliest gynecologic malignancy and the fifth most frequent cause of cancer-related mortality in women in the USA. Since DNA repair alterations are regarded as the "the Achille's heel" of HGSOC, both DNA homologous recombination and DNA mismatch repair deficiencies have been explored and targeted in epithelial ovarian cancers in the latest years. In this review, we aim at focusing on the therapeutic issues deriving from a faulty DNA repair machinery in epithelial ovarian cancers, starting from existing and well-established treatments and investigating new therapeutic approaches which could possibly improve ovarian cancer patients' survival outcomes in the near future. In particular, we concentrate on the role of both Poly (ADP-ribose) Polymerase (PARP) inhibitors (PARPis) and immune checkpoint inhibitors in HGSOC, highlighting their activity in relation to BRCA1/2 mutational status and homologous recombination deficiency (HRD). We investigate the biological rationale supporting their use in the clinical setting, pointing at tracking their route from the laboratory bench to the patient's bedside. Finally, we deal with the onset of mechanisms of primary and acquired resistance to PARPis, reporting the pioneering strategies aimed at converting homologous-recombination (HR) proficient tumors into homologous recombination (HR)-deficient HGSOC.
    Language English
    Publishing date 2020-05-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12051315
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Translational Research in Ovarian Cancer.

    Di Renzo, Maria Flavia / Valabrega, Giorgio

    Cancers

    2020  Volume 12, Issue 12

    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 [ ... ]. ...

    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 [...].
    Language English
    Publishing date 2020-12-08
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12123676
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action, Pharmacology, Safety, and Efficacy.

    Valabrega, Giorgio / Scotto, Giulia / Tuninetti, Valentina / Pani, Arianna / Scaglione, Francesco

    International journal of molecular sciences

    2021  Volume 22, Issue 8

    Abstract: Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) are able to interact with the binding site for PARP cofactor (NAD+) and trapping PARP on the DNA. In this way, they ... ...

    Abstract Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) are able to interact with the binding site for PARP cofactor (NAD+) and trapping PARP on the DNA. In this way, they inhibit single-strand DNA damage repair. These drugs have been approved in recent years for the treatment of ovarian cancer. Although they share some similarities, from the point of view of the chemical structure and pharmacodynamic, pharmacokinetic properties, these drugs also have some substantial differences. These differences may underlie the different safety profiles and activity of PARPi.
    MeSH term(s) Female ; Humans ; Ovarian Neoplasms/drug therapy ; Phthalazines/adverse effects ; Phthalazines/therapeutic use ; Piperazines/adverse effects ; Piperazines/therapeutic use ; Poly(ADP-ribose) Polymerase Inhibitors/adverse effects ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
    Chemical Substances Phthalazines ; Piperazines ; Poly(ADP-ribose) Polymerase Inhibitors ; olaparib (WOH1JD9AR8)
    Language English
    Publishing date 2021-04-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22084203
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Immunotherapy for Cervical Cancer: Are We Ready for Prime Time?

    Turinetto, Margherita / Valsecchi, Anna A / Tuninetti, Valentina / Scotto, Giulia / Borella, Fulvio / Valabrega, Giorgio

    International journal of molecular sciences

    2022  Volume 23, Issue 7

    Abstract: The prognosis of invasive cervical cancer (CC) remains poor, with a treatment approach that has remained the same for several decades. Lately, a better understanding of the interactions between the disease and the host immune system has allowed ... ...

    Abstract The prognosis of invasive cervical cancer (CC) remains poor, with a treatment approach that has remained the same for several decades. Lately, a better understanding of the interactions between the disease and the host immune system has allowed researchers to focus on the employment of immune therapy in various clinical settings. The most advanced strategy is immune checkpoint inhibitors (ICIs) with numerous phase II and III trials recently concluded with very encouraging results, assessing single agent therapy, combinations with chemotherapy and radiotherapy. Apart from ICIs, several other compounds have gained the spotlight. Tumor Infiltrating Lymphocytes (TILs) due to their highly selective tumoricidal effect and manageable adverse effect profile have received the FDA's Breakthrough Therapy designation in 2019. The antibody drug conjugate (ADC) Tisotumab-Vedotin has shown activity in metastatic CC relapsed after at least one line of chemotherapy, with a phase III trial currently actively enrolling patients. Moreover, the deeper understanding of the ever-changing immune landscape of CC carcinogenesis has resulted in the development of active therapeutic vaccines. This review highlights the different immunotherapeutic strategies being explored reflects on what role immunotherapy might have in therapeutic algorithms of CC and addresses the role of predictive biomarkers.
    MeSH term(s) Female ; Humans ; Immunoconjugates/therapeutic use ; Immunotherapy/methods ; Lymphocytes, Tumor-Infiltrating/pathology ; Uterine Cervical Neoplasms/pathology
    Chemical Substances Immunoconjugates
    Language English
    Publishing date 2022-03-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23073559
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Ovarian Cancer Immunotherapy: Turning up the Heat.

    Ghisoni, Eleonora / Imbimbo, Martina / Zimmermann, Stefan / Valabrega, Giorgio

    International journal of molecular sciences

    2019  Volume 20, Issue 12

    Abstract: Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies. Despite surgery and chemotherapy, 5-years survival rates have improved only modestly over the past few decades remaining at 45% for advanced stages. Therefore, ...

    Abstract Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies. Despite surgery and chemotherapy, 5-years survival rates have improved only modestly over the past few decades remaining at 45% for advanced stages. Therefore, novel therapies are urgently needed. The presence of tumor-infiltrating lymphocytes (TILs) in OC tumor microenvironment (TME) has already proved to be correlated with overall survival (OS), while immune evasion mechanisms are associated with poor prognosis. Although these data indicate that immunotherapy has a strong rationale in OC, single agent immune-checkpoints inhibitors (ICIs) have shown only modest results in this malignancy. In this review, we will discuss immune-targeting combination therapies and adoptive cell therapy (ACT), highlighting the challenges represented by these strategies, which aim at disrupting the stroma-tumor barrier to boost immune system against ovarian cancer.
    MeSH term(s) Animals ; Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/therapeutic use ; Biomarkers, Tumor ; Clinical Trials as Topic ; Combined Modality Therapy ; Female ; Humans ; Immunotherapy/methods ; Immunotherapy, Adoptive ; Lymphocytes, Tumor-Infiltrating/drug effects ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/metabolism ; Molecular Targeted Therapy ; Ovarian Neoplasms/immunology ; Ovarian Neoplasms/pathology ; Ovarian Neoplasms/therapy ; T-Lymphocyte Subsets/drug effects ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology
    Chemical Substances Antineoplastic Agents, Immunological ; Biomarkers, Tumor
    Language English
    Publishing date 2019-06-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms20122927
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Lynch syndrome-associated endometrial cancer patient with a rare novel germline likely pathogenic variant of MSH2 gene: A case report.

    Zumstein, L / Tuninetti, V / Vaira, M / Siatis, D / Palermo, F / Petracchini, M / Scotto, G / Turinetto, M / Piva, R / Pasini, B / Valabrega, G

    Gynecologic oncology reports

    2023  Volume 48, Page(s) 101220

    Abstract: The Lynch syndrome (LS) is an autosomal dominant condition usually characterized by germline pathogenic variants in DNA mismatch repair (MMR) genes. Despite the guidelines now available, determining the pathogenicity of rare variants remains challenging, ...

    Abstract The Lynch syndrome (LS) is an autosomal dominant condition usually characterized by germline pathogenic variants in DNA mismatch repair (MMR) genes. Despite the guidelines now available, determining the pathogenicity of rare variants remains challenging, as the clinical significance of a genetic variant could be uncertain, but it may represent a disease-associated variation in the aforementioned genes. In this case report we will describe the case of a 47 years-old female affected by endometrial cancer (EC) with an extremely rare germline heterozygous variant in the MSH2 gene (c.562G > T p. (Glu188Ter), exon 3) that is likely pathogenic, and a family history consistent with LS.
    Language English
    Publishing date 2023-06-16
    Publishing country Netherlands
    Document type Case Reports
    ZDB-ID 2818505-5
    ISSN 2352-5789
    ISSN 2352-5789
    DOI 10.1016/j.gore.2023.101220
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Ovarian Cancer Cells in Ascites Form Aggregates That Display a Hybrid Epithelial-Mesenchymal Phenotype and Allows Survival and Proliferation of Metastasizing Cells.

    Capellero, Sonia / Erriquez, Jessica / Battistini, Chiara / Porporato, Roberta / Scotto, Giulia / Borella, Fulvio / Di Renzo, Maria F / Valabrega, Giorgio / Olivero, Martina

    International journal of molecular sciences

    2022  Volume 23, Issue 2

    Abstract: Peritoneal metastases are the leading cause of morbidity and mortality in ovarian cancer. Cancer cells float in peritoneal fluid, named ascites, together with a definitely higher number of non neo-neoplastic cells, as single cells or multicellular ... ...

    Abstract Peritoneal metastases are the leading cause of morbidity and mortality in ovarian cancer. Cancer cells float in peritoneal fluid, named ascites, together with a definitely higher number of non neo-neoplastic cells, as single cells or multicellular aggregates. The aim of this work is to uncover the features that make these aggregates the metastasizing units. Immunofluorescence revealed that aggregates are made almost exclusively of ovarian cancer cells expressing the specific nuclear PAX8 protein. The same cells expressed epithelial and mesenchymal markers, such as EPCAM and αSMA, respectively. Expression of fibronectin further supported a hybrid epithelia-mesenchymal phenotype, that is maintained when aggregates are cultivated and proliferate. Hematopoietic cells as well as macrophages are negligible in the aggregates, while abundant in the ascitic fluid confirming their prominent role in establishing an eco-system necessary for the survival of ovarian cancer cells. Using ovarian cancer cell lines, we show that cells forming 3D structures neo-expressed thoroughly fibronectin and αSMA. Functional assays showed that αSMA and fibronectin are necessary for the compaction and survival of 3D structures. Altogether these data show that metastasizing units display a hybrid phenotype that allows maintenance of the 3D structures and the plasticity necessary for implant and seeding into peritoneal lining.
    MeSH term(s) Ascites/pathology ; Biomarkers, Tumor ; Cell Culture Techniques ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Epithelial-Mesenchymal Transition/genetics ; Female ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Neoplasm Metastasis ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Phenotype ; Tumor Cells, Cultured
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2022-01-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23020833
    Database MEDical Literature Analysis and Retrieval System OnLINE

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