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Source: Molecular Cancer Therapeutics
Cancer: Ovarian Cancer
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Total 11 results found since Jan 2013.
Abstract B04: RAD51 expression as a biomarker of homologous recombination deficiency in ovarian cancer
RAD51 is a critical component of the homologous recombination pathway, forming a nucleoprotein filament that enables strand exchange and templated error-free DNA repair. The tumor suppressors BRCA1 and BRCA2 interact with RAD51 to control its activity on DNA. Defects in homologous recombination in tumors are clinically relevant, with evidence of synthetic lethality of such cancers to poly ADP ribose polymerase (PARP) inhibitors.Mutations in RAD51 are uncommon in cancer, but aberrant over-expression of RAD51 has been reported as a mechanism to overcome a recombination defect in in-vitro models. However there are no large sc...
Source: Molecular Cancer Therapeutics - October 2, 2017 Category: Cancer & Oncology Authors: Hoppe, M. M., Tan, D. S., Lim, D. G., Karnezis, A., Huntsman, D., Steel, J., Liu, X., Paul, J., Lewsley, L.-A., Siddiqui, N., Brown, R., Jeyasekharan, A. D. Tags: New Technology and Bioinformatics: Poster Presentations - Proffered Abstracts Source Type: research
Abstract A15: Downregulation of c-myc is synthetic lethal with PARP inhibitors in high MYC cancers independent of BRCA status
In conclusion, we demonstrated that dual CDK + PARP inhibition is synthetic lethal in both BRCA wild-type and mutant TNBC cell lines and is dependent upon down regulation of c-myc. This study supports c-myc as predictor of response to PARP inhibitor therapy and may also serve as a biomarker of response to Dinaciclib + PARPi therapy in high MYC expressing tumors.Citation Format: Jason PW Carey, Smruthi Vjayaraghavan, Kelly Hunt, Khandan Keyomarsi. Downregulation of c-myc is synthetic lethal with PARP inhibitors in high MYC cancers independent of BRCA status [abstract]. In: Proceedings of the AACR Precision Medicine Series: ...
Source: Molecular Cancer Therapeutics - October 2, 2017 Category: Cancer & Oncology Authors: Carey, J. P., Vjayaraghavan, S., Hunt, K., Keyomarsi, K. Tags: Finding Synthetic Lethal Interactions through Functional Genomics: Poster Presentations - Proffered Abstracts Source Type: research
HSP70 Inhibition Synergistically Enhances the Effects of Magnetic Fluid Hyperthermia in Ovarian Cancer
Hyperthermia has been investigated as a potential treatment for cancer. However, specificity in hyperthermia application remains a significant challenge. Magnetic fluid hyperthermia (MFH) may be an alternative to surpass such a challenge, but implications of MFH at the cellular level are not well understood. Therefore, the present work focused on the examination of gene expression after MFH treatment and using such information to identify target genes that when inhibited could produce an enhanced therapeutic outcome after MFH. Genomic analyzes were performed using ovarian cancer cells exposed to MFH for 30 minutes at 43&de...
Source: Molecular Cancer Therapeutics - May 2, 2017 Category: Cancer & Oncology Authors: Court, K. A., Hatakeyama, H., Wu, S. Y., Lingegowda, M. S., Rodriguez-Aguayo, C., Lopez-Berestein, G., Ju-Seog, L., Rinaldi, C., Juan, E. J., Sood, A. K., Torres-Lugo, M. Tags: Models and Technologies Source Type: research
Dasatinib/ARID1A Synthetic Lethality in OCCC
New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based drug screens in OCCC tumor cell models, we have identified a synthetic lethal (SL) interaction between the kinase inhibitor dasatinib and a key driver in OCCC, ARID1A mutation. Imposing ARID1A deficiency upon a variety of human or mouse cells induced dasatinib sensitivity, both in vitro and in vivo, suggesting that this is a robust synthetic lethal interaction. The sensitivity of ARID1A-deficient cells to ...
Source: Molecular Cancer Therapeutics - July 4, 2016 Category: Cancer & Oncology Authors: Miller, R. E., Brough, R., Bajrami, I., Williamson, C. T., McDade, S., Campbell, J., Kigozi, A., Rafiq, R., Pemberton, H., Natrajan, R., Joel, J., Astley, H., Mahoney, C., Moore, J. D., Torrance, C., Gordan, J. D., Webber, J. T., Levin, R. S., Shokat, K. Tags: Small Molecule Therapeutics Source Type: research
Cyclin-Dependent Kinase 11 and Ovarian Cancer
Ovarian cancer is currently the most lethal gynecologic malignancy with limited treatment options. Improved targeted therapies are needed to combat ovarian cancer. Here, we report the identification of cyclin-dependent kinase 11 (CDK11) as a mediator of tumor cell growth and proliferation in ovarian cancer cells. Although CDK11 has not been implicated previously in this disease, we have found that its expression is upregulated in human ovarian cancer tissues and associated with malignant progression. Metastatic and recurrent tumors have significantly higher CDK11 expression when compared with the matched, original primary ...
Source: Molecular Cancer Therapeutics - July 4, 2016 Category: Cancer & Oncology Authors: Liu, X., Gao, Y., Shen, J., Yang, W., Choy, E., Mankin, H., Hornicek, F. J., Duan, Z. Tags: Cancer Biology and Signal Transduction Source Type: research
Abstract C155: Cyclin-dependent kinase 1 (Cdk1) is a promising therapeutic target to overcome ovarian cancer
Conclusions: Cdk1 is a promising gene for targeted anticancer therapy. It is expected that combined treatment with Cdk1 inhibitor and chemotherapeutic agents would maximize the effects of ovarian cancer treatment.Citation Format: Hanbyoul Cho, Wookyeom Yang, Ha-Yeon Shin, Eun-ju Lee, Doo-Byung Chay, Jae-Hoon Kim. Cyclin-dependent kinase 1 (Cdk1) is a promising therapeutic target to overcome ovarian cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C155.
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Cho, H., Yang, W., Shin, H.-Y., Lee, E.-j., Chay, D.-B., Kim, J.-H. Tags: Target Identification and Validation: Poster Presentations - Proffered Abstracts Source Type: research
Abstract A25: Molecular characterization of cyclin-dependent kinase 1 pathway in newly established epithelial ovarian cancer cell lines
Conclusions: These results suggest that elevated expression of Cdk1/cyclinB1 is important to EOC development and progression, providing new insight into the biology of EOC.Citation Format: Hanbyoul Cho, Assel Sabrgaliyeva, Woo Kyeom Yang, Sol Kim, Ha-Yeon Shin, Eun Ju Lee, Jae-hoon Kim. Molecular characterization of cyclin-dependent kinase 1 pathway in newly established epithelial ovarian cancer cell lines. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 ...
Source: Molecular Cancer Therapeutics - December 6, 2015 Category: Cancer & Oncology Authors: Cho, H., Sabrgaliyeva, A., Yang, W. K., Kim, S., Shin, H.-Y., Lee, E. J., Kim, J.-h. Tags: Biomarkers / Novel Imaging to Assess Response: Poster Presentations - Proffered Abstracts Source Type: research
Targeting c-MYC in Ovarian Cancer
The purpose of this study was to investigate the molecular and therapeutic effects of siRNA-mediated c-MYC silencing in cisplatin-resistant ovarian cancer. Statistical analysis of patient's data extracted from The Cancer Genome Atlas (TCGA) portal showed that the disease-free (DFS) and the overall (OS) survival were decreased in ovarian cancer patients with high c-MYC mRNA levels. Furthermore, analysis of a panel of ovarian cancer cell lines showed that c-MYC protein levels were higher in cisplatin-resistant cells when compared with their cisplatin-sensitive counterparts. In vitro cell viability, growth, cell-cycle progres...
Source: Molecular Cancer Therapeutics - October 5, 2015 Category: Cancer & Oncology Authors: Reyes-Gonzalez, J. M., Armaiz-Pena, G. N., Mangala, L. S., Valiyeva, F., Ivan, C., Pradeep, S., Echevarria-Vargas, I. M., Rivera-Reyes, A., Sood, A. K., Vivas-Mejia, P. E. Tags: Small Molecule Therapeutics Source Type: research
Abstract A36: Combined inhibition of PI3K isoforms and mTOR kinase is critical for cancer stem cell inhibition by VS-5584
We report here that VS-5584 is up to 30-fold more potent at inhibiting the proliferation and survival of CSCs than non-CSCs in breast cancer cell lines using multiple orthogonal CSC assays. Moreover, VS-5584 preferentially induced apoptosis in Aldefluor-positive CSCs relative to Aldefluor-negative non-CSCs as measured by Annexin V and Caspase 3/7 assays. In contrast, paclitaxel induced more apoptosis in non-CSCs than CSCs cells. VS-5584 also preferentially diminished CSCs in human breast and small cell lung cancer xenograft models in vivo, as evidenced by marked reduction of tumor-initiating capacity in an in vivo limiting...
Source: Molecular Cancer Therapeutics - July 6, 2015 Category: Cancer & Oncology Authors: Kolev, V. N., Wright, Q. G., Weaver, D. T., Padval, M. V., Pachter, J. A., Xu, Q. Tags: Preclinical and Clinical Studies in Breast Cancer: Poster Presentations - Proffered Abstracts Source Type: research
Cosilencing PKM-2 and MDR-1 in Ovarian Cancer
In this study, siRNA duplexes against pyruvate kinase M2 and multidrug resistance gene-1 were encapsulated in hyaluronic acid–based self-assembling nanoparticles. The particles were characterized for morphology, size, charge, encapsulation efficiency, and transfection efficiency. In vivo studies included biodistribution assessment, gene knockdown confirmation, therapeutic efficacy, and safety analysis. The benefit of active targeting of cancer cells was confirmed by modifying the particles' surface with a peptide targeted to epidermal growth factor receptor, which is overexpressed on the membranes of the SKOV-3 cance...
Source: Molecular Cancer Therapeutics - July 6, 2015 Category: Cancer & Oncology Authors: Talekar, M., Ouyang, Q., Goldberg, M. S., Amiji, M. M. Tags: Small Molecule Therapeutics Source Type: research
Multifunctional Micelles for the Reversal of Drug Resistance
Ovarian cancer is a dreadful disease estimated to be the second most common gynecologic malignancy worldwide. Its current therapy, based on cytoreductive surgery followed by the combination of platinum and taxanes, is frequently complicated by the onset of multidrug resistance (MDR). The discovery that survivin, a small antiapoptotic protein, is involved in chemoresistance provided a new prospect to overcome MDR in cancer, because siRNA could be used to inhibit the expression of survivin in cancer cells. With this in mind, we have developed self-assembly polymeric micelles (PM) able to efficiently co-load an anti–sur...
Source: Molecular Cancer Therapeutics - April 9, 2015 Category: Cancer & Oncology Authors: Salzano, G., Navarro, G., Trivedi, M. S., De Rosa, G., Torchilin, V. P. Tags: Models and Technologies Source Type: research
