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Source: Molecular Cancer Therapeutics
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Total 96 results found since Jan 2013.
Abstract B166: A RNA helicase siRNA screen to identify potential therapeutic targets in castration-resistant prostate cancer
Castration-resistant prostate cancers (CRPC) are resistant to androgen-deprivation therapies commonly used to treat carcinoma of the prostate, resulting in death from this disease. CRPC can remain AR-driven through upregulation of the expression of wild-type, mutated or alternatively spliced constitutively active AR. Targeting both full-length AR and AR splice variants may overcome endocrine resistance. Since RNA helicases play crucial roles in various aspects of RNA metabolism including transcription, pre-mRNA splicing, translation, RNA export and RNA decay, we evaluated potentially druggable RNA helicases implicated in t...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Wang, H., de Billy, E., de Bono, J., Workman, P. Tags: Target Identification and Validation: Poster Presentations - Proffered Abstracts Source Type: research
Abstract C171: Human anti-Nucleolin recombinant immunoagents as new potential tools for melanoma treatment
Immunotherapy and immune-based anti-cancer molecules represent a valid strategy to fight cancer. However, the choice of tumor-specific surface molecules for the selective targeting of cancer cells still represents a critical step in the study design for the development of new therapeutic approaches. Notably, the development of phage-display technology for the selection of fully human single chain antibody fragments (scFvs) and complete antibodies directed toward tumor-associated antigens has represented a significant advancement for immunotherapy.Nucleolin (NCL) is one of the most abundant non-ribosomal proteins in the nuc...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Braddom, A., Richmond, T., Sheetz, T., Reese, E., Tessari, A., Tober, K., Burd, C. E., De Lorenzo, C., Martin, E. W., Coppola, V., Tweedle, M. F., Oberyszyn, T., Croce, C. M., Palmieri, D. Tags: Therapeutic Agents: Biological: Poster Presentations - Proffered Abstracts Source Type: research
Abstract C178: TAS4464, a novel NEDD8 activating enzyme inhibitor, potently induces cell death via both intrinsic and extrinsic apoptotic pathways in acute myeloid leukemia
CONCLUSION: TAS4464 exerts a strong apoptosis-inducing effect in AML cell lines via both intrinsic and extrinsic apoptotic pathway by modulating apoptosis-related proteins. In addition, TAS4464 demonstrates marked antitumor activity in the THP-1 xenograft model. Given its potent preclinical activities, TAS4464 is a promising agent for treating AML.Citation Format: Hiroaki Ochiiwa, Chihoko Yoshimura, Hiromi Muraoka, Keiji Ishida, Tomonori Haruma, Shingo Tsuji, Akihiro Hashimoto, Takashi Mizutani, Shuichi Ohkubo, Kenichi Matsuo, Teruhiro Utsugi, Yoshikazu Iwasawa. TAS4464, a novel NEDD8 activating enzyme inhibitor, potently ...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Ochiiwa, H., Yoshimura, C., Muraoka, H., Ishida, K., Haruma, T., Tsuji, S., Hashimoto, A., Mizutani, T., Ohkubo, S., Matsuo, K., Utsugi, T., Iwasawa, Y. Tags: Therapeutic Agents: Other: Poster Presentations - Proffered Abstracts Source Type: research
Abstract C195: A Wee1 inhibitor analog of AZD1775 demonstrates synergy with cisplatin with reduced single-agent toxicity in medulloblastoma
Medulloblastoma is the most common primary brain tumor in children. Current treatment for medulloblastoma includes surgical resection, radiation and cytotoxic chemotherapy. Although this approach has improved survival rates, the high doses of chemotherapy required to circumvent drug resistance mechanisms and result in clinical efficacy often give rise to lasting neurocognitive defects, stunted growth, deafness, and even secondary tumors. Therefore, synergistic drug combinations that maintain clinical efficacy, but allow dose reductions of cytotoxic agents limiting their adverse effects would be an attractive approach for p...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Matheson, C. J., Venkataraman, S., Amani, V., Harris, P., Backos, D. S., Foreman, N. K., Vibhakar, R., Reigan, P. Tags: Therapeutic Agents: Small Molecule Kinase Inhibitors: Poster Presentations - Proffered Abstracts Source Type: research
Abstract B15: In vivo analysis of repeated siRNA silencing on protein expression levels
This study focused on determining the possibility of resistance development against siRNA treatment as a result of repeated exposure to siRNA in vivo. Our preliminary experiments in vitro revealed an unaffected siRNA cellular internalization and reproducible silencing efficiency of selected targets. The expression level of other mediators involved in breast cancer cell survival and proliferation (notably survivin, JUN, JAK2, NFkB and STAT3) were, however, altered in siRNA treated cells. In vivo experiments in a xenograft model demonstrated a similar silencing efficiency at the mRNA level after each repeated dose, with litt...
Source: Molecular Cancer Therapeutics - December 6, 2015 Category: Cancer & Oncology Authors: Aliabadi, H. M., Mahdipoor, P., Uludag, H. Tags: Other Combination Therapies: 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
Systemic PSMA-Targeted IR Sensitization
Radiation therapy is a highly effective tool for treating all stages of prostate cancer, from curative approaches in localized disease to palliative care and enhanced survival for patients with distant bone metastases. The therapeutic index of these approaches may be enhanced with targeted radiation-sensitizing agents. Aptamers are promising nucleic acid delivery agents for short interfering RNAs (siRNA) and short hairpin RNAs (shRNA). We have previously developed a radiation-sensitizing RNA aptamer–shRNA chimera that selectively delivers DNA-PK targeting shRNAs to prostate-specific membrane antigen (PSMA) positive c...
Source: Molecular Cancer Therapeutics - December 6, 2015 Category: Cancer & Oncology Authors: Ni, X., Zhang, Y., Zennami, K., Castanares, M., Mukherjee, A., Raval, R. R., Zhou, H., DeWeese, T. L., Lupold, S. E. Tags: Large Molecule Therapeutics Source Type: research
Abstract A07: Knockdown laminin-511 expression blocked endlthelial cell function in vitro and angiogenesis in vivo knockout skin model
In conclusion, our data suggested a possible involvement of laminin-511 in integrin alphaV and beta3-dependent angiogenesis and blood vessel maturation. Our works revealed the important roles of laminin-511 in endothelial cell activities, which proved its significance for angiogenesis.Citation Format: Jie Li, Tengjiao Cui. Knockdown laminin-511 expression blocked endlthelial cell function in vitro and angiogenesis in vivo knockout skin model. [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...
Source: Molecular Cancer Therapeutics - December 6, 2015 Category: Cancer & Oncology Authors: Li, J., Cui, T. Tags: Antiangiogenic Therapy: Poster Presentations - Proffered Abstracts Source Type: research
ABCB1 Inhibition Overcomes Resistance to MET Inhibitors
In this study, we tried to identify the mechanism of acquired resistance to MET inhibitors. We analyzed the antitumor effects of two MET inhibitors, PHA-665752 and crizotinib, in 10 NSCLC cell lines. EBC-1 cells with MET amplification were the only cells that were sensitive to both MET inhibitors. We established PHA-665752–resistant EBC-1 cells, namely EBC-1R cells. Activation of KRAS, EGFR, and FGFR2 signaling was observed in EBC-1R cells by FISH and receptor tyrosine kinase phosphorylation antibody arrays. EBC-1R cells also showed overexpression of ATP-binding cassette subfamily B member 1 (ABCB1) as well as phosph...
Source: Molecular Cancer Therapeutics - November 3, 2015 Category: Cancer & Oncology Authors: Sugano, T., Seike, M., Noro, R., Soeno, C., Chiba, M., Zou, F., Nakamichi, S., Nishijima, N., Matsumoto, M., Miyanaga, A., Kubota, K., Gemma, A. Tags: Small Molecule Therapeutics 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
EpCAM Aptamer-siRNAs for Targeted Breast Cancer Treatment
Effective therapeutic strategies for in vivo siRNA delivery to knockdown genes in cells outside the liver are needed to harness RNA interference for treating cancer. EpCAM is a tumor-associated antigen highly expressed on common epithelial cancers and their tumor-initiating cells (TIC, also known as cancer stem cells). Here, we show that aptamer–siRNA chimeras (AsiC, an EpCAM aptamer linked to an siRNA sense strand and annealed to the siRNA antisense strand) are selectively taken up and knock down gene expression in EpCAM+ cancer cells in vitro and in human cancer biopsy tissues. PLK1 EpCAM-AsiCs inhibit colony and m...
Source: Molecular Cancer Therapeutics - October 5, 2015 Category: Cancer & Oncology Authors: Gilboa-Geffen, A., Hamar, P., Le, M. T. N., Wheeler, L. A., Trifonova, R., Petrocca, F., Wittrup, A., Lieberman, J. Tags: Large Molecule Therapeutics Source Type: research
STAT1 and Cisplatin/Cetuximab in HNSCC
Cisplatin is a cytotoxic chemotherapeutic drug frequently used to treat many solid tumors, including head and neck squamous cell carcinoma (HNSCC). EGF receptor (EGFR) inhibitors have also shown efficacy as alternatives to cisplatin in some situations. However, large clinical trials have shown no added survival benefit from the use of these two drugs in combination. Possible explanations for this include overlapping downstream signaling cascades. Using in vitro studies, we tested the hypothesis that cisplatin and EGFR inhibitors rely on the activation of the tumor suppressor STAT1, characterized by its phosphorylation at s...
Source: Molecular Cancer Therapeutics - September 2, 2015 Category: Cancer & Oncology Authors: Schmitt, N. C., Trivedi, S., Ferris, R. L. Tags: Cancer Biology and Signal Transduction Source Type: research
Ingenol Mebutate's Mechanism in Keratinocytes
In conclusion, we have shown that ingenol mebutate–induced cell death is mediated through the PKC/MEK/ERK pathway, and we have functionally linked the downstream induction of IL1R2 and IL13RA2 expression to the reduced viability of ingenol mebutate–treated cells. Mol Cancer Ther; 14(9); 2132–42. ©2015 AACR.
Source: Molecular Cancer Therapeutics - September 2, 2015 Category: Cancer & Oncology Authors: Freiberger, S. N., Cheng, P. F., Iotzova-Weiss, G., Neu, J., Liu, Q., Dziunycz, P., Zibert, J. R., Dummer, R., Skak, K., Levesque, M. P., Hofbauer, G. F. L. Tags: Cancer Biology and Signal Transduction Source Type: research
MCL-1 Is a Key Determinant of Breast Cancer Cell Survival
Hyperexpression of antiapoptotic BCL-2 family proteins allows cells to survive despite the receipt of signals that would ordinarily induce their deletion, a facet frequently exploited by tumors. Tumors addicted to the BCL-2 family proteins for survival are now being targeted therapeutically. For example, navitoclax, a BCL-2/BCL-XL/BCL-W inhibitor, is currently in phase I/II clinical trials in numerous malignancies. However, the related family member, MCL-1, limits the efficacy of navitoclax and other chemotherapeutic agents. In the present study, we identify breast cancer cell lines that depend upon MCL-1 for survival and ...
Source: Molecular Cancer Therapeutics - August 5, 2015 Category: Cancer & Oncology Authors: Xiao, Y., Nimmer, P., Sheppard, G. S., Bruncko, M., Hessler, P., Lu, X., Roberts-Rapp, L., Pappano, W. N., Elmore, S. W., Souers, A. J., Leverson, J. D., Phillips, D. C. Tags: Small Molecule Therapeutics Source Type: research
TMPRSS2-ERG Fusion Inhibits NHEJ DNA Repair
We reported that radiosensitization by a PARP inhibitor (PARPi) was highly prominent in prostate cancer cells expressing the TMPRSS2–ERG gene fusion protein. Here, we show that TMPRSS2–ERG blocks nonhomologous end-joining (NHEJ) DNA repair by inhibiting DNA-PKcs. VCaP cells, which harbor TMPRSS2–ERG and PC3 cells that stably express it, displayed H2AX and 53BP1 foci constitutively, indicating persistent DNA damage that was absent if TMPRSS2–ERG was depleted by siRNA in VCaP cells. The extent of DNA damage was enhanced and associated with TMPRSS2–ERG's ability to inhibit DNA-PKcs function, as i...
Source: Molecular Cancer Therapeutics - August 5, 2015 Category: Cancer & Oncology Authors: Chatterjee, P., Choudhary, G. S., Alswillah, T., Xiong, X., Heston, W. D., Magi-Galluzzi, C., Zhang, J., Klein, E. A., Almasan, A. Tags: Cancer Biology and Signal Transduction Source Type: research
