10th Anniversary of Cancers—Targeted Therapies for Ovarian Cancer Treatment from Bench to Bedside

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

Deadline for manuscript submissions: closed (31 December 2018) | Viewed by 42122

Special Issue Editors


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Guest Editor
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: gynecologic cancers; tumor microenvironment; diagnostic and prognostic biomarkers discovery; stomal-epithelial interaction; exosomes
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Guest Editor
Division of Surgery, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: gynecologic cancers; novel therapeutics; clinical trial design

Special Issue Information

Dear Colleagues,

This year, we are celebrating the 10th anniversary of our journal, Cancers. To date, the journal has published more than 1000 papers and the journal website attracts more than 60,000 monthly visits. The journal has an Impact Factor 5.326 (2017, ranks Q1: 44/222) and a CiteScore 5.82 (2017). This milestone cannot be achieved without our readers, authors, peer reviewers, editors, and all the people working for the journal who have joined their tremendous efforts for years.

To mark this important milestone, a Special Issue entitled “10th Anniversary of Cancers—Targeted Therapies for Ovarian Cancer Treatment from Bench to Bedside” is being launched. This Special Issue collects high quality research articles and review papers on the topic related to the latest development of targeted cancer therapy in ovarian cancer. We kindly encourage all research groups to submit up-to-date, and comprehensive reviews and your research findings on this topic.

Prof. Dr. Samuel C. Mok
Prof. Dr. Robert Coleman
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 short 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.

Published Papers (6 papers)

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Research

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14 pages, 3112 KiB  
Article
DIRAS3-Derived Peptide Inhibits Autophagy in Ovarian Cancer Cells by Binding to Beclin1
by Margie N. Sutton, Gilbert Y. Huang, Xiaowen Liang, Rajesh Sharma, Albert S. Reger, Weiqun Mao, Lan Pang, Philip J. Rask, Kwangkook Lee, Joshua P. Gray, Amy M. Hurwitz, Timothy Palzkill, Steven W. Millward, Choel Kim, Zhen Lu and Robert C. Bast, Jr.
Cancers 2019, 11(4), 557; https://doi.org/10.3390/cancers11040557 - 18 Apr 2019
Cited by 14 | Viewed by 4626
Abstract
Autophagy can protect cancer cells from acute starvation and enhance resistance to chemotherapy. Previously, we reported that autophagy plays a critical role in the survival of dormant, drug resistant ovarian cancer cells using human xenograft models and correlated the up-regulation of autophagy and [...] Read more.
Autophagy can protect cancer cells from acute starvation and enhance resistance to chemotherapy. Previously, we reported that autophagy plays a critical role in the survival of dormant, drug resistant ovarian cancer cells using human xenograft models and correlated the up-regulation of autophagy and DIRAS3 expression in clinical samples obtained during “second look” operations. DIRAS3 is an imprinted tumor suppressor gene that encodes a 26 kD GTPase with homology to RAS that inhibits cancer cell proliferation and motility. Re-expression of DIRAS3 in ovarian cancer xenografts also induces dormancy and autophagy. DIRAS3 can bind to Beclin1 forming the Autophagy Initiation Complex that triggers autophagosome formation. Both the N-terminus of DIRAS3 (residues 15–33) and the switch II region of DIRAS3 (residues 93–107) interact directly with BECN1. We have identified an autophagy-inhibiting peptide based on the switch II region of DIRAS3 linked to Tat peptide that is taken up by ovarian cancer cells, binds Beclin1 and inhibits starvation-induced DIRAS3-mediated autophagy. Full article
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17 pages, 4845 KiB  
Article
A Cell-Autonomous Oncosuppressive Role of Human RNASET2 Affecting ECM-Mediated Oncogenic Signaling
by Francesca Roggiani, Cristina Riva, Francesco Raspagliesi, Giovanni Porta, Roberto Valli, Roberto Taramelli, Francesco Acquati, Delia Mezzanzanica and Antonella Tomassetti
Cancers 2019, 11(2), 255; https://doi.org/10.3390/cancers11020255 - 22 Feb 2019
Cited by 9 | Viewed by 3497
Abstract
RNASET2 is an extracellular ribonuclease endowed with a marked antitumorigenic role in several carcinomas, independent from its catalytic activity. Besides its antitumorigenic role by the recruitment to the tumor mass of immune cells from the monocyte/macrophage lineage, RNASET2 is induced by cellular stress [...] Read more.
RNASET2 is an extracellular ribonuclease endowed with a marked antitumorigenic role in several carcinomas, independent from its catalytic activity. Besides its antitumorigenic role by the recruitment to the tumor mass of immune cells from the monocyte/macrophage lineage, RNASET2 is induced by cellular stress and involved in actin cytoskeleton remodeling affecting cell interactions with the extracellular matrix (ECM). Here, we aimed to investigate the effects of RNASET2 expression modulation on cell phenotype and behavior in epithelial ovarian cancer (EOC) cellular models. In silico analysis on two publicly available datasets of gene expression from EOC patients (n = 392) indicated that increased RNASET2 transcript levels are associated with longer overall survival. In EOC biopsies (n = 101), analyzed by immunohistochemistry, RNASET2 was found heterogeneously expressed among tumors with different clinical–pathological characteristics and, in some cases, its expression localized to tumor-associated ECM. By characterizing in vitro two models of EOC cells in which RNASET2 was silenced or overexpressed, we report that RNASET2 expression negatively affects growth capability by conferring a peculiar cell phenotype upon the interaction of EOC cells with the ECM, resulting in decreased src activation. Altogether, these data suggest that drugs targeting activated src might represent a therapeutic approach for RNASET2-expressing EOCs. Full article
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16 pages, 2193 KiB  
Article
Ovarian Cancer Relies on Glucose Transporter 1 to Fuel Glycolysis and Growth: Anti-Tumor Activity of BAY-876
by Yibao Ma, Wei Wang, Michael O. Idowu, Unsong Oh, Xiang-Yang Wang, Sarah M. Temkin and Xianjun Fang
Cancers 2019, 11(1), 33; https://doi.org/10.3390/cancers11010033 - 31 Dec 2018
Cited by 96 | Viewed by 9221
Abstract
The recent progresses in understanding of cancer glycolytic phenotype have offered new strategies to manage ovarian cancer and other malignancies. However, therapeutic targeting of glycolysis to treat cancer remains unsuccessful due to complex mechanisms of tumor glycolysis and the lack of selective, potent [...] Read more.
The recent progresses in understanding of cancer glycolytic phenotype have offered new strategies to manage ovarian cancer and other malignancies. However, therapeutic targeting of glycolysis to treat cancer remains unsuccessful due to complex mechanisms of tumor glycolysis and the lack of selective, potent and safe glycolytic inhibitors. Recently, BAY-876 was identified as a new-generation inhibitor of glucose transporter 1 (GLUT1), a GLUT isoform commonly overexpressed but functionally poorly defined in ovarian cancer. Notably, BAY-876 has not been evaluated in any cell or preclinical animal models since its discovery. We herein took advantage of BAY-876 and molecular approaches to study GLUT1 regulation, targetability, and functional relevance to cancer glycolysis. The anti-tumor activity of BAY-876 was evaluated with ovarian cancer cell line- and patient-derived xenograft (PDX) models. Our results show that inhibition of GLUT1 is sufficient to block basal and stress-regulated glycolysis, and anchorage-dependent and independent growth of ovarian cancer cells. BAY-876 dramatically inhibits tumorigenicity of both cell line-derived xenografts and PDXs. These studies provide direct evidence that GLUT1 is causally linked to the glycolytic phenotype in ovarian cancer. BAY-876 is a potent blocker of GLUT1 activity, glycolytic metabolism and ovarian cancer growth, holding promise as a novel glycolysis-targeted anti-cancer agent. Full article
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Review

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25 pages, 3031 KiB  
Review
Photoimmunotherapy of Ovarian Cancer: A Unique Niche in the Management of Advanced Disease
by Shubhankar Nath, Mohammad Ahsan Saad, Michael Pigula, Joseph W.R. Swain and Tayyaba Hasan
Cancers 2019, 11(12), 1887; https://doi.org/10.3390/cancers11121887 - 27 Nov 2019
Cited by 31 | Viewed by 5140
Abstract
Ovarian cancer (OvCa) is the leading cause of gynecological cancer-related deaths in the United States, with five-year survival rates of 15–20% for stage III cancers and 5% for stage IV cancers. The standard of care for advanced OvCa involves surgical debulking of disseminated [...] Read more.
Ovarian cancer (OvCa) is the leading cause of gynecological cancer-related deaths in the United States, with five-year survival rates of 15–20% for stage III cancers and 5% for stage IV cancers. The standard of care for advanced OvCa involves surgical debulking of disseminated disease in the peritoneum followed by chemotherapy. Despite advances in treatment efficacy, the prognosis for advanced stage OvCa patients remains poor and the emergence of chemoresistant disease localized to the peritoneum is the primary cause of death. Therefore, a complementary modality that is agnostic to typical chemo- and radio-resistance mechanisms is urgently needed. Photodynamic therapy (PDT), a photochemistry-based process, is an ideal complement to standard treatments for residual disease. The confinement of the disease in the peritoneal cavity makes it amenable for regionally localized treatment with PDT. PDT involves photochemical generation of cytotoxic reactive molecular species (RMS) by non-toxic photosensitizers (PSs) following exposure to non-harmful visible light, leading to localized cell death. However, due to the complex topology of sensitive organs in the peritoneum, diffuse intra-abdominal PDT induces dose-limiting toxicities due to non-selective accumulation of PSs in both healthy and diseased tissue. In an effort to achieve selective damage to tumorous nodules, targeted PS formulations have shown promise to make PDT a feasible treatment modality in this setting. This targeted strategy involves chemical conjugation of PSs to antibodies, referred to as photoimmunoconjugates (PICs), to target OvCa specific molecular markers leading to enhanced therapeutic outcomes while reducing off-target toxicity. In light of promising results of pilot clinical studies and recent preclinical advances, this review provides the rationale and methodologies for PIC-based PDT, or photo-immunotherapy (PIT), in the context of OvCa management. Full article
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26 pages, 3708 KiB  
Review
PI3K-AKT-mTOR and NFκB Pathways in Ovarian Cancer: Implications for Targeted Therapeutics
by Alia Ghoneum and Neveen Said
Cancers 2019, 11(7), 949; https://doi.org/10.3390/cancers11070949 - 5 Jul 2019
Cited by 108 | Viewed by 13646
Abstract
Ovarian cancer is the most lethal gynecologic malignancy in the United States, with an estimated 22,530 new cases and 13,980 deaths in 2019. Recent studies have indicated that the phosphoinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), as well as [...] Read more.
Ovarian cancer is the most lethal gynecologic malignancy in the United States, with an estimated 22,530 new cases and 13,980 deaths in 2019. Recent studies have indicated that the phosphoinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), as well as the nuclear factor-κ light chain enhancer of activated B cells (NFκB) pathways are highly mutated and/or hyper-activated in a majority of ovarian cancer patients, and are associated with advanced grade and stage disease and poor prognosis. In this review, we will investigate PI3K/AKT/mTOR and their interconnection with NFκB pathway in ovarian cancer cells. Full article
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15 pages, 577 KiB  
Review
Review: Targeting the Transforming Growth Factor-Beta Pathway in Ovarian Cancer
by Brandon M. Roane, Rebecca C. Arend and Michael J. Birrer
Cancers 2019, 11(5), 668; https://doi.org/10.3390/cancers11050668 - 14 May 2019
Cited by 43 | Viewed by 5118
Abstract
Despite extensive efforts, there has been limited progress in optimizing treatment of ovarian cancer patients. The vast majority of patients experience recurrence within a few years despite a high response rate to upfront therapy. The minimal improvement in overall survival of ovarian cancer [...] Read more.
Despite extensive efforts, there has been limited progress in optimizing treatment of ovarian cancer patients. The vast majority of patients experience recurrence within a few years despite a high response rate to upfront therapy. The minimal improvement in overall survival of ovarian cancer patients in recent decades has directed research towards identifying specific biomarkers that serve both as prognostic factors and targets for therapy. Transforming Growth Factor-β (TGF-β) is a superfamily of proteins that have been well studied and implicated in a wide variety of cellular processes, both in normal physiologic development and malignant cellular growth. Hypersignaling via the TGF-β pathway is associated with increased tumor dissemination through various processes including immune evasion, promotion of angiogenesis, and increased epithelial to mesenchymal transformation. This pathway has been studied in various malignancies, including ovarian cancer. As targeted therapy has become increasingly prominent in drug development and clinical research, biomarkers such as TGF-β are being studied to improve outcomes in the ovarian cancer patient population. This review article discusses the role of TGF-β in ovarian cancer progression, the mechanisms of TGF-β signaling, and the targeted therapies aimed at the TGF-β pathway that are currently being studied. Full article
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