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Novel Therapeutic Strategies for Gynecological Cancer: Molecular Biological Insights

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (20 April 2025) | Viewed by 11432

Special Issue Editor


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Guest Editor
College of Medicine, Taipei Medical University, Taipei 110, Taiwan
Interests: cancer; HPV; structural biology

Special Issue Information

Dear Colleagues,

Gynecological cancers, including those of the ovaries, cervix, uterus, fallopian tubes, and vulva, pose significant challenges in clinical management and treatment. Despite advances in traditional therapies such as surgery, chemotherapy, and radiation, the recurrence rates and mortality associated with these cancers remain substantial. In recent years, there has been a growing interest in exploring novel therapeutic strategies that target molecular pathways involved in the development and progression of gynecological malignancies. These approaches offer promising avenues for more effective and personalized treatment options. Here, we delve into some of the key molecular biological insights driving these novel therapeutic strategies.

Molecular biological insights have paved the way for the development of novel therapeutic strategies that promise to transform the landscape of gynecological cancer treatment. Targeted therapies, immunotherapy, epigenetic modulators, and personalized medicine approaches offer new hope for improving patient outcomes and advancing towards the goal of precision oncology in the management of gynecological malignancies.

The present Special Issue, entitled “Novel Therapeutic Strategies for Gynecological Cancer: Molecular Biological Insights”, aims to present recent research developments to the wider community involved in this field. We welcome contributions in this field.

Dr. Jiantai Timothy Qiu
Guest Editor

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Keywords

  • gynecological cancers
  • cervical cancer
  • uterine cancer
  • ovarian cancer
  • fallopian tube cancer
  • peritoneal cancer and vulvar cancer
  • targeted therapy
  • immunotherapy
  • epigenetic modulator
  • cancer vaccines and cell therapy
  • molecular profiling and personalized medicine

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Published Papers (4 papers)

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Research

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17 pages, 6245 KiB  
Article
Trastuzumab-Mediated Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Enhances Natural Killer Cell Cytotoxicity in HER2-Overexpressing Ovarian Cancer
by Sa Deok Hong, Nar Bahadur Katuwal, Min Sil Kang, Mithun Ghosh, Seong Min Park, Tae Hoen Kim, Young Seok Baek, Seung Ryeol Lee and Yong Wha Moon
Int. J. Mol. Sci. 2024, 25(21), 11733; https://doi.org/10.3390/ijms252111733 - 31 Oct 2024
Cited by 3 | Viewed by 3114
Abstract
Ovarian cancer is the deadliest gynecologic cancer. Although human epidermal growth factor receptor-2 (HER2) overexpression, a poor prognostic molecular marker in ovarian cancer, is found in almost 30% of ovarian cancer cases, there are no established therapies for HER2-overexpressing ovarian cancer. In this [...] Read more.
Ovarian cancer is the deadliest gynecologic cancer. Although human epidermal growth factor receptor-2 (HER2) overexpression, a poor prognostic molecular marker in ovarian cancer, is found in almost 30% of ovarian cancer cases, there are no established therapies for HER2-overexpressing ovarian cancer. In this study, we investigated the efficacy of combined samfenet, a biosimilar compound of trastuzumab, and natural killer (NK) cells in preclinical model of HER2-overexpressing ovarian cancer. Firstly, we screened the HER2 expression in three ovarian cancer cell lines and eight ovarian cancer patient-derived tumor xenograft (PDTX) samples. Then, immunohistochemistry and silver in situ hybridization (SISH) were performed following clinical criteria. HER2-overexpressing cells exhibited the highest sensitivity to samfenet compared with low-HER2-expressing cells. In addition, the combination of samfenet with natural killer (NK) cells resulted in significantly enhanced sensitivity to HER2-overexpressing cells and showed a significant antitumor effect on PDTX mice compared with monotherapy. It is known that anti-HER2-humanized IgG1 monoclonal antibodies, including trastuzumab, induce antibody-dependent cellular cytotoxicity (ADCC). Consequently, the combination of samfenet with NK cells demonstrated NK cell-mediated ADCC, as confirmed using an in vitro NK cytotoxicity assay and in vivo antitumor efficacy. A transferase dUTP nick end labeling (TUNEL) assay using xenografted tumors further supported the ADCC effects based on the increase in the number of apoptotic cells in the combination group. Furthermore, high HER2 expression was associated with shorter progression-free survival and overall survival based on public mRNA expression data. In this study, we demonstrated that the combination of samfenet and NK cell therapy could be a promising treatment strategy for patients with HER2-overexpressing ovarian cancer, through ADCC effects. Therefore, this study supports a rationale for further clinical studies of the combination of samfenet and NK cells as a therapy for patients with HER2-overexpressing ovarian cancer. Full article
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13 pages, 2330 KiB  
Article
Subgroup Analysis of TLR2, -3, -4 and -8 in Relation to the Severity of Clinical Manifestations of Cervical HPV Infection
by Alexander Dushkin, Maxim Afanasiev, Stanislav Afanasiev, Tatiana Grishacheva, Elena Biryukova, Irina Dushkina and Alexander Karaulov
Int. J. Mol. Sci. 2024, 25(17), 9719; https://doi.org/10.3390/ijms25179719 - 8 Sep 2024
Cited by 1 | Viewed by 1363
Abstract
We present the findings of assessing the expression levels of extracellular TLR2 and TLR4 and intracellular TLR3 and TLR8 correlating with the severity of clinical manifestations of HPV infection. A total of 199 women took part in a single-center prospective comparative research study [...] Read more.
We present the findings of assessing the expression levels of extracellular TLR2 and TLR4 and intracellular TLR3 and TLR8 correlating with the severity of clinical manifestations of HPV infection. A total of 199 women took part in a single-center prospective comparative research study on TLR2, TLR3, TLR4 and TLR8 expression in HPV-related cervical lesions. TLRs’ mRNA expression was analyzed using real-time reverse transcription polymerase chain reaction (RT-PCR). Our results indicate the potential significance of TLR3, TLR4 and TLR8 in responding to HPV infection and its progression to SILs and CC, highlighting the importance of HPV polyinfection in relation to TLR4 and TLR8. Full article
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22 pages, 2884 KiB  
Article
Molecular Mechanisms Underlying the Anticancer Properties of Pitavastatin against Cervical Cancer Cells
by Ya-Hui Chen, Jyun-Xue Wu, Shun-Fa Yang, Yun-Chia Wu and Yi-Hsuan Hsiao
Int. J. Mol. Sci. 2024, 25(14), 7915; https://doi.org/10.3390/ijms25147915 - 19 Jul 2024
Cited by 1 | Viewed by 2461
Abstract
Cervical cancer ranks as the fourth most prevalent form of cancer and is a significant contributor to female mortality on a global scale. Pitavastatin is an anti-hyperlipidemic medication and has been demonstrated to exert anticancer and anti-inflammatory effects. Thus, the purpose of this [...] Read more.
Cervical cancer ranks as the fourth most prevalent form of cancer and is a significant contributor to female mortality on a global scale. Pitavastatin is an anti-hyperlipidemic medication and has been demonstrated to exert anticancer and anti-inflammatory effects. Thus, the purpose of this study was to evaluate the anticancer effect of pitavastatin on cervical cancer and the underlying molecular mechanisms involved. The results showed that pitavastatin significantly inhibited cell viability by targeting cell-cycle arrest and apoptosis in Ca Ski, HeLa and C-33 A cells. Pitavastatin caused sub-G1- and G0/G1-phase arrest in Ca Ski and HeLa cells and sub-G1- and G2/M-phase arrest in C-33 A cells. Moreover, pitavastatin induced apoptosis via the activation of poly-ADP-ribose polymerase (PARP), Bax and cleaved caspase 3; inactivated the expression of Bcl-2; and increased mitochondrial membrane depolarization. Furthermore, pitavastatin induced apoptosis and slowed the migration of all three cervical cell lines, mediated by the PI3K/AKT and MAPK (JNK, p38 and ERK1/2) pathways. Pitavastatin markedly inhibited tumor growth in vivo in a cancer cell-originated xenograft mouse model. Overall, our results identified pitavastatin as an anticancer agent for cervical cancer, which might be expanded to clinical use in the future. Full article
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Review

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16 pages, 649 KiB  
Review
The Impact of Neoadjuvant Chemotherapy on Ovarian Cancer Tumor Microenvironment: A Systematic Review of the Literature
by Giulia Spagnol, Eleonora Ghisoni, Matteo Morotti, Orazio De Tommasi, Matteo Marchetti, Sofia Bigardi, Valentina Tuninetti, Giulia Tasca, Marco Noventa, Carlo Saccardi, Roberto Tozzi and Denarda Dangaj Laniti
Int. J. Mol. Sci. 2024, 25(13), 7070; https://doi.org/10.3390/ijms25137070 - 27 Jun 2024
Cited by 7 | Viewed by 3453
Abstract
Immunotherapy, particularly the use of immune checkpoint inhibitors (ICIs), has shown limited efficacy in treating ovarian cancer (OC), possibly due to diverse T cell infiltration patterns in the tumor microenvironment. This review explores how neoadjuvant chemotherapy (NACT) impacts the immune landscape of OC, [...] Read more.
Immunotherapy, particularly the use of immune checkpoint inhibitors (ICIs), has shown limited efficacy in treating ovarian cancer (OC), possibly due to diverse T cell infiltration patterns in the tumor microenvironment. This review explores how neoadjuvant chemotherapy (NACT) impacts the immune landscape of OC, focusing on tumor-infiltrating lymphocytes (TILs), PD-1/PD-L1 expression, and their clinical implications. A comprehensive literature search across four databases yielded nine relevant studies. These studies evaluated stromal (sTILs) and intra-epithelial (ieTILs) TILs before and after NACT. sTIL responses varied, impacting prognostic outcomes, and ieTILs increased in some patients without clear survival associations. PD-L1 expression after NACT correlated with improved overall survival (OS), and increases in granzyme B+ and PD-1 correlated with longer progression-free survival (PFS). Remarkably, reduced FoxP3+ TILs post-NACT correlated with better prognosis. NACT often increases sTIL/ieTIL and CD8+ subpopulations, but their correlation with improved PFS and OS varies. Upregulation of co-inhibitory molecules, notably PD-L1, suggests an immunosuppressive response to chemotherapy. Ongoing trials exploring neoadjuvant ICIs and chemotherapy offer promise for advancing OC treatment. Standardized measurements assessing TIL density, location, and heterogeneity are crucial for addressing genetic complexity and immunological heterogeneity in OC. Full article
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