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Cancers
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Gynecologic Cancers: Clinical and Translational Research
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Gynecologic Cancers: Clinical and Translational Research

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

Deadline for manuscript submissions: closed (1 February 2022) | Viewed by 16020

Special Issue Editors

Dr. Thomas P. Conrads

E-Mail Website
Guest Editor
Women's Service Line, Inova Health System, Annandale, VA 22003, USA
Interests: translational proteogenomics; tumor microenvironment; cancer biomarkers
Dr. George Larry Maxwell

E-Mail Website
Guest Editor
Women's Service Line, Inova Health System, Annandale, VA 22003, USA
Interests: clinical care and management of women with gynecologic cancers

Special Issue Information

Dear Colleagues,

Cancer accounts for 14% of all deaths among women, second only to cardiovascular disease, among which gynecologic cancers account for approximately 20% of the estimated 6.7 million new cancer cases and 3.5 million deaths. Apart from the human toll of these dreadful diseases, according to the Agency for Healthcare and Quality Research, over USD 5 billion per year is spent in the US alone on the inpatient treatment of patients with gynecologic tumors, a cost that exceeds the inpatient treatment costs for females with cancers of the breast, lung, or colon. These cost estimates do not include the costs of gynecologic cancer screening, outpatient treatment or the costs associated with loss of productivity because of time away from work. A great deal of effort from clinical and translational research has begun to provide insights into identifying molecular alterations associated with gynecologic cancer for development of novel and cost-effective early detection, prevention, and treatment strategies to improve patient outcome. This Special Issue will highlight the current state of the art in clinical and translational efforts in gynecologic cancer research and future prospects for improving patient outcomes.

Dr. Thomas P. Conrads
Dr. George Larry Maxwell
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

  • ovarian
  • uterine corpus
  • gynecologic
  • cancer
  • proteogenomics
  • tissue microenvironment

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Published Papers (5 papers)

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20 pages, 2051 KiB  
Article
Improving Risk Assessment for Metastatic Disease in Endometrioid Endometrial Cancer Patients Using Molecular and Clinical Features: An NRG Oncology/Gynecologic Oncology Group Study
by Yovanni Casablanca, Guisong Wang, Heather A. Lankes, Chunqiao Tian, Nicholas W. Bateman, Caela R. Miller, Nicole P. Chappell, Laura J. Havrilesky, Amy Hooks Wallace, Nilsa C. Ramirez, David S. Miller, Julie Oliver, Dave Mitchell, Tracy Litzi, Brian E. Blanton, William J. Lowery, John I. Risinger, Chad A. Hamilton, Neil T. Phippen, Thomas P. Conrads, David Mutch, Katherine Moxley, Roger B. Lee, Floor Backes, Michael J. Birrer, Kathleen M. Darcy and George Larry Maxwelladd Show full author list remove Hide full author list
Cancers 2022, 14(17), 4070; https://doi.org/10.3390/cancers14174070 - 23 Aug 2022
Cited by 1 | Viewed by 2475
Abstract
Objectives: A risk assessment model for metastasis in endometrioid endometrial cancer (EEC) was developed using molecular and clinical features, and prognostic association was examined. Methods: Patients had stage I, IIIC, or IV EEC with tumor-derived RNA-sequencing or microarray-based data. Metastasis-associated transcripts and platform-centric [...] Read more.
Objectives: A risk assessment model for metastasis in endometrioid endometrial cancer (EEC) was developed using molecular and clinical features, and prognostic association was examined. Methods: Patients had stage I, IIIC, or IV EEC with tumor-derived RNA-sequencing or microarray-based data. Metastasis-associated transcripts and platform-centric diagnostic algorithms were selected and evaluated using regression modeling and receiver operating characteristic curves. Results: Seven metastasis-associated transcripts were selected from analysis in the training cohorts using 10-fold cross validation and incorporated into an MS7 classifier using platform-specific coefficients. The predictive accuracy of the MS7 classifier in Training-1 was superior to that of other clinical and molecular features, with an area under the curve (95% confidence interval) of 0.89 (0.80–0.98) for MS7 compared with 0.69 (0.59–0.80) and 0.71 (0.58–0.83) for the top evaluated clinical and molecular features, respectively. The performance of MS7 was independently validated in 245 patients using RNA sequencing and in 81 patients using microarray-based data. MS7 + MI (myometrial invasion) was preferrable to individual features and exhibited 100% sensitivity and negative predictive value. The MS7 classifier was associated with lower progression-free and overall survival (p ≤ 0.003). Conclusion: A risk assessment classifier for metastasis and prognosis in EEC patients with primary tumor derived MS7 + MI is available for further development and optimization as a companion clinical support tool. Full article
(This article belongs to the Special Issue Gynecologic Cancers: Clinical and Translational Research)
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15 pages, 1749 KiB  
Article
Molecular Correlates of Venous Thromboembolism (VTE) in Ovarian Cancer
by Deanna Glassman, Nicholas W. Bateman, Sanghoon Lee, Li Zhao, Jun Yao, Yukun Tan, Cristina Ivan, Kelly M. Rangel, Jianhua Zhang, Kelly A. Conrads, Brian L. Hood, Tamara Abulez, P. Andrew Futreal, Nicole D. Fleming, Vahid Afshar-Kharghan, George L. Maxwell, Thomas P. Conrads, Ken Chen and Anil K. Sood
Cancers 2022, 14(6), 1496; https://doi.org/10.3390/cancers14061496 - 15 Mar 2022
Cited by 13 | Viewed by 3359
Abstract
Background: The incidence of venous thromboembolism (VTE) in patients with ovarian cancer is higher than most solid tumors, ranging between 10–30%, and a diagnosis of VTE in this patient population is associated with worse oncologic outcomes. The tumor-specific molecular factors that may lead [...] Read more.
Background: The incidence of venous thromboembolism (VTE) in patients with ovarian cancer is higher than most solid tumors, ranging between 10–30%, and a diagnosis of VTE in this patient population is associated with worse oncologic outcomes. The tumor-specific molecular factors that may lead to the development of VTE are not well understood. Objectives: The aim of this study was to identify molecular features present in ovarian tumors of patients with VTE compared to those without. Methods: We performed a multiplatform omics analysis incorporating RNA and DNA sequencing, quantitative proteomics, as well as immune cell profiling of high-grade serous ovarian carcinoma (HGSC) samples from a cohort of 32 patients with or without VTE. Results: Pathway analyses revealed upregulation of both inflammatory and coagulation pathways in the VTE group. While DNA whole-exome sequencing failed to identify significant coding alterations between the groups, the results of an integrated proteomic and RNA sequencing analysis indicated that there is a relationship between VTE and the expression of platelet-derived growth factor subunit B (PDGFB) and extracellular proteins in tumor cells, namely collagens, that are correlated with the formation of thrombosis. Conclusions: In this comprehensive analysis of HGSC tumor tissues from patients with and without VTE, we identified markers unique to the VTE group that could contribute to development of thrombosis. Our findings provide additional insights into the molecular alterations underlying the development of VTE in ovarian cancer patients and invite further investigation into potential predictive biomarkers of VTE in ovarian cancer. Full article
(This article belongs to the Special Issue Gynecologic Cancers: Clinical and Translational Research)
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11 pages, 3291 KiB  
Article
CX-5461 Treatment Leads to Cytosolic DNA-Mediated STING Activation in Ovarian Cancer
by Robert Cornelison, Kuntal Biswas, Danielle C. Llaneza, Alexandra R. Harris, Nisha G. Sosale, Matthew J. Lazzara and Charles N. Landen
Cancers 2021, 13(20), 5056; https://doi.org/10.3390/cancers13205056 - 9 Oct 2021
Cited by 12 | Viewed by 3355
Abstract
Epithelial ovarian cancer (EOC) is the deadliest of the gynecologic malignancies, with an overall survival rate of <30%. Recent research has suggested that targeting RNA polymerase I (POL I) with small-molecule inhibitors may be a viable therapeutic approach to combating EOC, even when [...] Read more.
Epithelial ovarian cancer (EOC) is the deadliest of the gynecologic malignancies, with an overall survival rate of <30%. Recent research has suggested that targeting RNA polymerase I (POL I) with small-molecule inhibitors may be a viable therapeutic approach to combating EOC, even when chemoresistance is present. CX-5461 is one of the most promising POL I inhibitors currently being investigated, and previous reports have shown that CX-5461 treatment induces DNA damage response (DDR) through ATM/ATR kinase. Investigation into downstream effects of CX-5461 led us to uncovering a previously unreported phenotype. Treatment with CX-5461 induces a rapid accumulation of cytosolic DNA. This accumulation leads to transcriptional upregulation of ‘STimulator of Interferon Genes’ (STING) in the same time frame, phosphorylation of IRF3, and activation of type I interferon response both in vitro and in vivo. This activation is mediated and dependent on cyclic GMP–AMP synthase (cGAS). Here, we show THAT CX-5461 leads to an accumulation of cytosolic dsDNA and thereby activates the cGAS–STING–TBK1–IRF3 innate immune pathway, which induces type I IFN. CX-5461 treatment-mediated immune activation may be a powerful mechanism of action to exploit, leading to novel drug combinations with a chance of increasing immunotherapy efficacy, possibly with some cancer specificity limiting deleterious toxicities. Full article
(This article belongs to the Special Issue Gynecologic Cancers: Clinical and Translational Research)
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11 pages, 3054 KiB  
Systematic Review
Tumor Budding in Gynecologic Cancer as a Marker for Poor Survival: A Systematic Review and Meta-Analysis of the Perspectives of Epithelial–Mesenchymal Transition
by Muhammad Joan Ailia, Nishant Thakur, Yosep Chong and Kwangil Yim
Cancers 2022, 14(6), 1431; https://doi.org/10.3390/cancers14061431 - 10 Mar 2022
Cited by 15 | Viewed by 2906
Abstract
This study aimed to assess the prognostic significance, assessment methods, and molecular features of tumor budding (TB). A literature search of Medline, EMBASE, Cochrane Library, and eleven cohort studies (seven cervical and four endometrial cancers) was conducted. Three assessment methods for TB involving [...] Read more.
This study aimed to assess the prognostic significance, assessment methods, and molecular features of tumor budding (TB). A literature search of Medline, EMBASE, Cochrane Library, and eleven cohort studies (seven cervical and four endometrial cancers) was conducted. Three assessment methods for TB involving 2009 patients were collected and constituted in the analysis. Our meta-analysis showed that TB was a marker of poor survival, regardless of the cancer origin site or assessment method (overall survival: hazard ratio [HR], 2.40; 95% confidence interval [CI], 1.82–3.17; disease-free survival: HR, 3.32; 95% CI, 2.46–4.48). In endometrial cancers, TB is associated with the epithelial–mesenchymal transition, microvessel density, and decreased hormone receptor expression. Thus, we suggest TB as a poor prognostic marker for all gynecologic cancers. Full article
(This article belongs to the Special Issue Gynecologic Cancers: Clinical and Translational Research)
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14 pages, 1572 KiB  
Systematic Review
Dose-Intense Cisplatin-Based Neoadjuvant Chemotherapy Increases Survival in Advanced Cervical Cancer: An Up-to-Date Meta-Analysis
by Van Tai Nguyen, Sabine Winterman, Margot Playe, Amélie Benbara, Laurent Zelek, Frédéric Pamoukdjian and Guilhem Bousquet
Cancers 2022, 14(3), 842; https://doi.org/10.3390/cancers14030842 - 8 Feb 2022
Cited by 19 | Viewed by 3058
Abstract
Purpose: We set out to demonstrate the benefit of using dose-intense cisplatin-based neoadjuvant chemotherapy in terms of overall survival and progression-free survival. Methods: We searched through MEDLINE and Cochrane Library databases up to May 2021 to identify randomized clinical trials comparing the benefit [...] Read more.
Purpose: We set out to demonstrate the benefit of using dose-intense cisplatin-based neoadjuvant chemotherapy in terms of overall survival and progression-free survival. Methods: We searched through MEDLINE and Cochrane Library databases up to May 2021 to identify randomized clinical trials comparing the benefit of using cisplatin-based neoadjuvant chemotherapy followed by local treatment with local treatment alone for the treatment of locally advanced cervical cancer. The PRISMA statement was applied. Results: Twenty-two randomized clinical trials were retrieved between 1991 and 2019, corresponding to 3632 women with FIGO stages IB2-IVA cervical cancer. More than 50% of the randomized clinical trials were assessed as having a low risk of bias. There was no benefit of neoadjuvant chemotherapy on overall survival, but there was significant heterogeneity across studies (I2 = 45%, p = 0.01). In contrast, dose-intense cisplatin at over 72.5 mg/m2/3 weeks was significantly associated with increased overall survival (RR = 0.87, p < 0.05) with no heterogeneity across the pooled studies (I2 = 36%, p = 0.11). The survival benefit was even greater when cisplatin was administered at a dose over 105 mg/m2/3 weeks (RR = 0.79, p < 0.05). Conclusion: Even though radiotherapy combined with weekly cisplatin-based chemotherapy remains standard of care for the treatment of locally advanced cervical cancer, our meta-analysis makes it possible to consider the use of dose-intense cisplatin-based neoadjuvant chemotherapy when local treatment is suboptimal and opens perspectives for designing new clinical trials in this setting. Neoadjuvant chemotherapy could be proposed when surgery is local treatment instead of standard chemoradiotherapy for the treatment of locally advanced cervical cancer. Full article
(This article belongs to the Special Issue Gynecologic Cancers: Clinical and Translational Research)
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