scholarly journals Therapeutic Strategies in Ovarian Cancer

Author(s):  
Dan Ancua ◽  
Octavian Neagoe ◽  
Rzvan Ilina ◽  
Adrian Carabineanu ◽  
Corina erban ◽  
...  
2019 ◽  
Vol 19 (6) ◽  
pp. 449-467
Author(s):  
Zhiquan Liang ◽  
Ziwen Lu ◽  
Yafei Zhang ◽  
Dongsheng Shang ◽  
Ruyan Li ◽  
...  

Ovarian cancer is a leading cause of death worldwide from gynecological malignancies, mainly because there are few early symptoms and the disease is generally diagnosed at an advanced stage. In addition, despite the effectiveness of cytoreductive surgery for ovarian cancer and the high response rates to chemotherapy, survival has improved little over the last 20 years. The management of patients with ovarian cancer also remains similar despite studies showing striking differences and heterogeneity among different subtypes. It is therefore clear that novel targeted therapeutics are urgently needed to improve clinical outcomes for ovarian cancer. To that end, several membrane receptors associated with pivotal cellular processes and often aberrantly overexpressed in ovarian cancer cells have emerged as potential targets for receptor-mediated therapeutic strategies including specific agents and multifunctional delivery systems based on ligand-receptor binding. This review focuses on the profiles and potentials of such strategies proposed for ovarian cancer treatment and imaging.


2020 ◽  
Vol 10 ◽  
Author(s):  
Nastassja Terraneo ◽  
Francis Jacob ◽  
Anna Dubrovska ◽  
Jürgen Grünberg

Oncotarget ◽  
2016 ◽  
Vol 0 (0) ◽  
Author(s):  
Lara Paracchini ◽  
Laura Mannarino ◽  
Ilaria Craparotta ◽  
Chiara Romualdi ◽  
Robert Fruscio ◽  
...  

2012 ◽  
Vol 31 (1) ◽  
pp. 14 ◽  
Author(s):  
Ayako Kim ◽  
Yutaka Ueda ◽  
Tetsuji Naka ◽  
Takayuki Enomoto

Reproduction ◽  
2021 ◽  
Vol 161 (1) ◽  
pp. R1-R11
Author(s):  
Griselda Irusta

Although ovarian cancer mortality rates have slightly declined in the last 40 years, ovarian cancer continues to be the eighth cause of cancer death in women. Ovarian cancer is characterized by its high response to treatments but also by its high rate of recurrence. Although treatments are limited to cytoreductive surgery and platinum-based chemotherapy, other therapies using antiangiogenic agents and poly (ADP-ribose) polymerase inhibitors are being tested. Nevertheless, these therapeutic strategies have had poor results and new potential targets and approaches are thus needed. The present review focuses on the recent evidence on antiangiogenic strategies in ovarian cancer cells and on the mechanisms governed by Notch and β-catenin proteins. It also describes the concept of ‘vascular normalization’ by using the platelet-derived growth factor, PDGFB, molecule as a tool to regulate ovarian tumor angiogenesis and thus improve ovarian tumor treatment. It has been reported that alterations in the Notch system components and changes in the canonical Wnt/β-catenin signaling, the other pathway of our interest, are relevant to molecular events that contribute to ovarian cancer development. Thus, in this review, we consider these aspects of the ovarian tumor biology as potential new therapeutic strategies for the treatment of this disease.


Life ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 8
Author(s):  
Daniela B. Vera ◽  
Allison N. Fredes ◽  
Maritza P. Garrido ◽  
Carmen Romero

Ovarian cancer is the most lethal gynecological neoplasm, and epithelial ovarian cancer (EOC) accounts for 90% of ovarian malignancies. The 5-year survival is less than 45%, and, unlike other types of cancer, the proportion of women who die from this disease has not improved in recent decades. Nerve growth factor (NGF) and tropomyosin kinase A (TRKA), its high-affinity receptor, play a crucial role in pathogenesis through cell proliferation, angiogenesis, invasion, and migration. NGF/TRKA increase their expression during the progression of EOC by upregulation of oncogenic proteins as vascular endothelial growth factor (VEGF) and c-Myc. Otherwise, the expression of most oncoproteins is regulated by microRNAs (miRs). Our laboratory group reported that the tumoral effect of NGF/TRKA depends on the regulation of miR-145 levels in EOC. Currently, mitochondria have been proposed as new therapeutic targets to activate the apoptotic pathway in the cancer cell. The mitochondria are involved in a myriad of functions as energy production, redox control, homeostasis of Ca+2, and cell death. We demonstrated that NGF stimulation produces an augment in the Bcl-2/BAX ratio, which supports the anti-apoptotic effects of NGF in EOC cells. The review aimed to discuss the role of mitochondria in the interplay between NGF/TRKA and miR-145 and possible therapeutic strategies that may decrease mortality due to EOC.


2021 ◽  
Author(s):  
Ofer Reizes ◽  
Tyler Alban ◽  
Max Horowitz ◽  
Danielle Chau ◽  
Zahraa Alali ◽  
...  

Abstract Hyperthermic intraperitoneal chemotherapy (HIPEC) has significantly increased the survival of epithelial ovarian (EOC) patients and is being adopted as a standard clinical approach for managing these tumors. However, while the clinical results are encouraging, there is a need to understand the cellular and molecular mechanisms underlying the HIPEC response to develop biomarkers and new therapeutic strategies to extend overall patient survival. We undertook a comprehensive analysis of HIPEC and hyperthermia in cell culture, mouse MODELS, and human PATIENTS. Ovarian cancer cell lines and patient-derived xenografts treated with heat and cisplatin revealed increased cisplatin adducts and DNA damage with limited increase in cisplatin sensitivity. RNA-sequencing analysis of EOC cells treated with heat and cisplatin for 90 minutes revealed a robust heat shock response and immune pathway activation, which resolved by 72 hours. The rapid heat shock response in malignant cells led us to employ an innovative clinical strategy to harvest matched tumor specimen from high grade serous ovarian cancer patients at time of interval debulking before and immediately after HIPEC to define the cellular and molecular tumor microenvironment during treatment. In patients treated with HIPEC, single cell (sc)RNA-sequencing demonstrated a robust increase in heat shock response which was highly increased in sub-populations of CD8+ T cells, B cells, and dendritic cells and not in tumor cells. Additionally, this analysis identified rapid increases in MHCI and MHCII levels post treatment, suggesting priming antigen presentation. Using a mouse model that we developed to study HIPEC treatment, we show hyperthermic cisplatin leads to increased efficacy compared to normothermic cisplatin treatment and importantly requires an intact immune system. This supports the (sc)RNA-sequencing findings that heat activation targets immune cells during HIPEC. Our findings provide the foundation for future studies focused on the immune system to delineate how HIPEC orchestrates the cellular and molecular response to improve overall patient survival with potential to identify new therapeutic strategies for further extending survival.


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