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Advances in Ovarian Cancer Research and Treatment: 2nd Edition

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 25 December 2025 | Viewed by 7355

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Dr. Maria Barbolina

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Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA
Interests: ovarian carcinoma; organ-specific metastasis; signal transduction; targets for treatment; chemoresistance
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Special Issue Information

Dear Colleagues,

This collection is the second edition of an existing Special Issue, titled “Advances in Ovarian Cancer Research and Treatment” (https://www.mdpi.com/journal/cancers/special_issues/Q35JY80Q7G).

Metastatic, chemotherapy-resistant, recurrent epithelial ovarian carcinoma remains one of the deadliest malignancies affecting women worldwide. It is a complex disease thought to arise from multiple cell types within the female reproductive tract. Several distinct histotypes of epithelial ovarian carcinoma exist, with the high-grade serous form being the most predominant and the deadliest. High-grade serous ovarian carcinoma is mainly disseminated transcoelomically, and patients succumb to metastases that form within the peritoneal cavity. A better understanding of the biology of these metastases and their responses to treatments from the perspective of the microenvironment at the organ sites within the peritoneal cavity and the cancer cells themselves could help with devising rational strategies for preventing or blocking recurrences. This Special Issue will highlight recent advances in the treatment of this deadly disease, as well as in research into the mechanisms of its metastasis and chemotherapy resistance.

Dr. Maria Barbolina
Guest Editor

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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 250 words) can be sent to the Editorial Office for assessment.

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Keywords

ovarian carcinoma metastasis
mechanisms of dissemination
chemotherapy resistance
novel treatments and therapeutic approaches
novel molecular targets

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Published Papers (4 papers)

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14 pages, 1587 KB

Open AccessArticle

Ovarian Cancer Ascites Enriched for CCL23 Reduces Macrophage-Derived CXCL10 Secretion and Is Associated with Poor Patient Outcomes

by Susan M. Lang, Supreeti Tallapragada, Justine Chan and Oliver Dorigo

Cancers 2025, 17(24), 3925; https://doi.org/10.3390/cancers17243925 - 8 Dec 2025

Viewed by 179

Abstract

Background: Ovarian cancer ascites contributes to the immunosuppressive tumor microenvironment (TME) via macrophage-derived chemokine ligand 23 (CCL23) signaling, T-cell exhaustion, and upregulating pro-inflammatory cytokines. However, the extent to which ascites-derived CCL23 concentrations associate with changes in pro- and anti-inflammatory cytokines and overall patient survival in ovarian cancer patients remains unknown. Methods: CCL23 concentrations and pro-inflammatory cytokines were measured from ascites of stage III and IV epithelial ovarian cancer patients by ELISA and Luminex assays, respectively. Kaplan–Meier survival analysis was performed using patient outcome data from Stanford University Hospital and the Cancer Genome Atlas. The impact of CCL23 peptides on pro-inflammatory cytokine secretion was evaluated in vitro using differentiated THP-1 monocytes. Results: A total of 40 patients were enrolled and CCL23 concentrations were detected in all ascites samples (median = 2.42 ng/mL; range [0.06–6.45]). Reduced survival time corresponded with high CCL23 containing samples (mOS: 3.2 years, [3.9 ng/mL]) versus intermediate (mOS: 6.0 years, [2.5 ng/mL]) or low (mOS: 5.9 years; [1.4 ng/mL]) groups. TGCA analysis of patient outcomes was confirmatory. A significant negative correlation was observed between high CCL23 ascites concentrations versus CXCL10 and soluble PD-1 cytokine levels. High tumor expression of CXCL10 was associated with improved survival (mOS; 5.9 years) versus low CXCL10 expression (mOS; 3.2 years). In vitro, CCL23-stimulated THP-1 macrophages exhibited reduced CXCL10 secretion via STAT-3 activation. Conclusions: High CCL23 concentrations in ovarian cancer ascites reduces CXCL10 secretion from myeloid cells and associates with reduced patient survival. Full article

(This article belongs to the Special Issue Advances in Ovarian Cancer Research and Treatment: 2nd Edition)

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19 pages, 5444 KB

Open AccessArticle

Synergistic Effects of Novel Xanthone Derivatives and Mild Hyperthermia in Ovarian Cancer: Insights from Gene Expression and In Silico Analyses

by Jakub Rech, Dorota Żelaszczyk, Henryk Marona and Ilona Anna Bednarek

Cancers 2025, 17(17), 2896; https://doi.org/10.3390/cancers17172896 - 3 Sep 2025

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Abstract

Background/Objectives: In the fight against ovarian cancer, various therapies have been employed, with a strong focus on developing novel derivatives of existing substances. Methods: In this study, we continue our research on novel xanthone derivatives in combination with mild hyperthermia, targeting ovarian cancer cell lines TOV-21G and SK-OV-3. Using qPCR arrays, we analyzed 84 cellular stress-related genes categorized into anti-oxidant and pro-oxidant enzymes, molecular chaperones, and xenobiotic metabolism including the cytochrome P450 group. Furthermore, we conducted in silico analyses to investigate the pathways of the most affected genes, gene set enrichment, and gene ontology. Results: The most significant changes were observed in SOD2, SOD3, CYP2F1, CYP1B1, and HMOX1. Additional changes related to drug toxicity and the postulated mechanism of action were also identified. Based on in silico analyses, we concluded that the primary node of hyperthermia-induced changes is HSPA1A. Heat-induced alterations predominantly revolve around misfolded proteins, monooxygenase activity, and ATPase activity. Conclusions: To summarize, the combined therapy of novel xanthone derivatives and mild hyperthermia shows promising results and warrants further investigation to fully elucidate the mechanisms of action underlying these effects. Full article

(This article belongs to the Special Issue Advances in Ovarian Cancer Research and Treatment: 2nd Edition)

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11 pages, 1064 KB

Open AccessArticle

The Association Between Location of BRCA Mutation and Efficacy of PARP Inhibitor as a Frontline Maintenance Therapy in Advanced Epithelial Ovarian Cancer

by Ji Hyun Kim, Se Ik Kim, Eun Taeg Kim, Hyeong In Ha, Dong-eun Lee, Yong Jae Lee, Jung-Yun Lee, Sunghoon Kim, Sang Wun Kim, Young Tae Kim, Sang-Yoon Park, Myong Cheol Lim and Eun-Ji Nam

Cancers 2025, 17(5), 756; https://doi.org/10.3390/cancers17050756 - 23 Feb 2025

Cited by 4 | Viewed by 2511

Abstract

Background: The location of BRCA mutations within functional domains may affect sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy. This study aimed to evaluate the progression-free survival (PFS) benefit from the PARP inhibitor in relation to the location of mutations in BRCA1/BRCA2 in newly diagnosed ovarian cancer. Materials and methods: Patients with advanced stage III-IV epithelial ovarian cancer who had deleterious BRCA1 or BRCA2 were analyzed. PFS and clinical and molecular data were compared between patients who received olaparib or niraparib as frontline maintenance therapy and those who did not. Subgroup analyses were conducted based on the location of BRCA mutations within the functional domain or the ovarian cancer cluster region (OCCR). Results: Of the 380 patients, 242 (63.7%) harbored BRCA1 mutation, 137 (36.1%) harbored BRCA2, and one (0.3%) harbored both BRCA1 and BRCA2. With a median follow-up of 35.8 months, the DNA binding domain in BRCA1 (HR, 0.34; 95% CI, 0.15–0.79; p = 0.01) and BRCA2 (HR, 0.25; 95% CI, 0.08–0.78; p = 0.01) demonstrated particularly significant benefit. In patients who harbored BRCA1 mutation in the C-terminal domain (BRCT), no statistically significant PFS benefit from PARP inhibitor was observed (HR, 0.76; 95% CI, 0.39–1.52; p = 0.44). PFS benefit from PARP inhibitor maintenance was observed in both OCCR (HR, 0.49; 95% CI, 0.32–0.74; p < 0.01) and non-OCCR (HR, 0.51; 95% CI, 0.27–0.63; p < 0.01). Conclusions: Frontline PARP inhibitor maintenance therapy demonstrated a significant PFS benefit in patients with BRCA1/2 mutations, with particularly pronounced benefits for those with mutations located in the DBD of BRCA1 and BRCA2. However, the benefit was less evident for patients with BRCA1 mutations located in the BRCT domain. Full article

(This article belongs to the Special Issue Advances in Ovarian Cancer Research and Treatment: 2nd Edition)

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Open AccessSystematic Review

Evaluating the Impact of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on Interval and Secondary Debulking in Ovarian Cancer: A Systematic Review

by Dimitrios Tsolakidis, Dimitrios Kyziridis, Theodoros Panoskaltsis, Apostolos Kalakonas, Vasileios Theodoulidis, Kimon Chatzistamatiou, Dimitrios Zouzoulas and Antonios-Apostolos Tentes

Cancers 2025, 17(5), 904; https://doi.org/10.3390/cancers17050904 - 6 Mar 2025

Cited by 1 | Viewed by 3315

Abstract

Background/Objectives: Hyperthermic intraperitoneal chemotherapy (HIPEC) was revealed as a promising adjunct to cytoreductive surgery (CRS) in the treatment of advanced epithelial ovarian cancer (EOC). This review evaluated the impact HIPEC had on survival outcomes, recurrence patterns and safety in patients that underwent HIPEC in conjunction with interval and secondary CRS for advanced and recurrent ovarian cancer. Methods: A thorough search was conducted using PubMed, Scopus, Cochrane Library, and Google Scholar to identify relevant studies published until 1 January 2025. The studies were assessed for survival outcomes, recurrence patterns, safety, and quality of life. The risk of bias was evaluated using the ROB 2 tool for randomized and ROBINS-I for non-randomized articles. The results are presented narratively, highlighting key findings, comparing results and assessing inconsistencies and limitations. Results: HIPEC demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS), particularly in cases with optimal cytoreduction (CC-0/CC-1). The recurrence patterns showed a reduction in peritoneal dissemination with HIPEC, although extraperitoneal recurrences were reported in some cases. Most studies reported comparable morbidity rates between HIPEC and non-HIPEC groups, with acceptable safety profiles. The variability in the HIPEC protocols and the limited quality-of-life and cost-effectiveness data were noteworthy limitations. Conclusions: HIPEC, when performed during interval or secondary CRS, offers survival benefits and can modify recurrence patterns in advanced EOC, although challenges related to protocol standardization, patient selection, and long-term outcomes persist. Future research should focus on multicenter trials with uniform protocols, long follow-up periods and patient-centered outcomes to further validate the role of HIPEC in clinical practice. Full article

(This article belongs to the Special Issue Advances in Ovarian Cancer Research and Treatment: 2nd Edition)

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