scholarly journals Current Status of Patient-Derived Ovarian Cancer Models

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 505 ◽  
Author(s):  
Yoshiaki Maru ◽  
Yoshitaka Hippo
Keyword(s):  
Ovarian Cancer ◽  
Current Status ◽  
Conventional Chemotherapy ◽  
Cancer Subtypes ◽  
Cancer Models ◽  
Generic Term ◽  
Frequent Failure ◽  
Effective Drugs ◽  
Therapeutic Responses

Ovarian cancer (OC) is one of the leading causes of female cancer death. Recent studies have documented its extensive variations as a disease entity, in terms of cell or tissue of origin, pre-cancerous lesions, common mutations, and therapeutic responses, leading to the notion that OC is a generic term referring to a whole range of different cancer subtypes. Despite such heterogeneity, OC treatment is stereotypic; aggressive surgery followed by conventional chemotherapy could result in chemo-resistant diseases. Whereas molecular-targeted therapies will become shortly available for a subset of OC, there still remain many patients without effective drugs, requiring development of groundbreaking therapeutic agents. In preclinical studies for drug discovery, cancer cell lines used to be the gold standard, but now this has declined due to frequent failure in predicting therapeutic responses in patients. In this regard, patient-derived cells and tumors are gaining more attention in precise and physiological modeling of in situ tumors, which could also pave the way to implementation of precision medicine. In this article, we comprehensively overviewed the current status of various platforms for patient-derived OC models. We highly appreciate the potentials of organoid culture in achieving high success rate and retaining tumor heterogeneity.

Molecular prognostic markers in ovarian cancer: toward patient-tailored therapy

2006 ◽  
Vol 16 (Suppl 1) ◽  
pp. 152-165 ◽  
Author(s):  
A. P.G. Crijns ◽  
E. W. Duiker ◽  
S. De Jong ◽  
P. H.B. Willemse ◽  
A. G.J. Van Der Zee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Throughput Screening ◽  
Protein Microarrays ◽  
Current Status ◽  
Molecular Heterogeneity ◽  
Cancer Subtypes ◽  
Specific Tumor ◽  
Single Marker ◽  
Profiling Techniques ◽  
Microarray Studies

In ovarian cancer the ceiling seems to be reached with chemotherapeutic drugs. Therefore a paradigm shift is needed. Instead of treating all patients according to standard guidelines, individualized molecular targeted treatment should be aimed for. This means that molecular profiles of the distinct ovarian cancer subtypes should be established. Until recently, most studies trying to identify molecular targets were single-marker studies. The prognostic role of key components of apoptotic and prosurvival pathways such as p53, EGFR, and HER2 has been extensively studied because resistance to chemotherapy is often caused by failure of tumor cells to go into apoptosis. However, it is more than likely that different ovarian cancer subtypes with extensive molecular heterogeneity exist. Therefore, exploration of the potential of specific tumor-targeted therapy, based on expression of a prognostic tumor profile, may be of interest. Recently, new profiling techniques, such as DNA and protein microarrays, have enabled high-throughput screening of tumors. In this review an overview of the current status of prognostic marker and molecular targeting research in ovarian cancer, including microarray studies, is presented.

Focal Adhesion Kinase in Ovarian Cancer: A Potential Therapeutic Target for Platinum and Taxane-Resistant Tumors

2019 ◽  
Vol 19 (3) ◽  
pp. 179-188 ◽  
Author(s):  
Arkene Levy ◽  
Khalid Alhazzani ◽  
Priya Dondapati ◽  
Ali Alaseem ◽  
Khadijah Cheema ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Tumor Stage ◽  
Current Status ◽  
Potential Therapeutic Target ◽  
Resistant Disease ◽  
Development Of Resistance ◽  
And Function ◽  
Mdr 1

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase, which is an essential player in regulating cell migration, invasion, adhesion, proliferation, and survival. Its overexpression and activation have been identified in sixty-eight percent of epithelial ovarian cancer patients and this is significantly associated with higher tumor stage, metastasis, and shorter overall survival of these patients. Most recently, a new role has emerged for FAK in promoting resistance to taxane and platinum-based therapy in ovarian and other cancers. The development of resistance is a complex network of molecular processes that make the identification of a targetable biomarker in platinum and taxane-resistant ovarian cancer a major challenge. FAK overexpression upregulates ALDH and XIAP activity in platinum-resistant and increases CD44, YB1, and MDR-1 activity in taxaneresistant tumors. FAK is therefore now emerging as a prognostically significant candidate in this regard, with mounting evidence from recent successes in preclinical and clinical trials using small molecule FAK inhibitors. This review will summarize the significance and function of FAK in ovarian cancer, and its emerging role in chemotherapeutic resistance. We will discuss the current status of FAK inhibitors in ovarian cancers, their therapeutic competencies and limitations, and further propose that the combination of FAK inhibitors with platinum and taxane-based therapies could be an efficacious approach in chemotherapeutic resistant disease.

scholarly journals Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mei Song ◽  
Oladapo O. Yeku ◽  
Sarwish Rafiq ◽  
Terence Purdon ◽  
Xue Dong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
P53 Protein ◽  
Cellular Adhesion ◽  
Cancer Growth ◽  
The Novel ◽  
Conventional Chemotherapy ◽  
Potential Therapeutic Target ◽  
Cancer Stemness ◽  
Tumor Associated Macrophage ◽  
Immunosuppressive Tumor Microenvironment

AbstractImmunosuppressive tumor microenvironment (TME) and ascites-derived spheroids in ovarian cancer (OC) facilitate tumor growth and progression, and also pose major obstacles for cancer therapy. The molecular pathways involved in the OC-TME interactions, how the crosstalk impinges on OC aggression and chemoresistance are not well-characterized. Here, we demonstrate that tumor-derived UBR5, an E3 ligase overexpressed in human OC associated with poor prognosis, is essential for OC progression principally by promoting tumor-associated macrophage recruitment and activation via key chemokines and cytokines. UBR5 is also required to sustain cell-intrinsic β-catenin-mediated signaling to promote cellular adhesion/colonization and organoid formation by controlling the p53 protein level. OC-specific targeting of UBR5 strongly augments the survival benefit of conventional chemotherapy and immunotherapies. This work provides mechanistic insights into the novel oncogene-like functions of UBR5 in regulating the OC-TME crosstalk and suggests that UBR5 is a potential therapeutic target in OC treatment for modulating the TME and cancer stemness.

scholarly journals Light-Up Probe for Targeted and Activatable Photodynamic Therapy with Real-Time In Situ Reporting of Sensitizer Activation and Therapeutic Responses

2015 ◽  
Vol 25 (42) ◽  
pp. 6586-6595 ◽  
Author(s):  
Youyong Yuan ◽  
Chong-Jing Zhang ◽  
Ryan T. K. Kwok ◽  
Shidang Xu ◽  
Ruoyu Zhang ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Real Time ◽  
Therapeutic Responses

scholarly journals An In Vitro and In Vivo Investigation of the Antimetastatic Effects of a Chinese Medicinal Decoction, Erxian Decoction, on Human Ovarian Cancer Models

2012 ◽  
Vol 12 (4) ◽  
pp. 336-346 ◽  
Author(s):  
Ellie S. M. Chu ◽  
Stephen C. W. Sze ◽  
Ho P. Cheung ◽  
Qing Liu ◽  
Tzi B. Ng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Human Ovarian Cancer ◽  
Erxian Decoction ◽  
Cancer Models
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