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Total 151 results found since Jan 2013.
Abstract B119: Blocking metabolic stress response with genetic knockdown and selective ligands of sigma-1 receptor in cancer cells
In this study we examined whether Sig1R sustains proliferation, survival and tumorigenic properties of human cancer cells. Knockdown of Sig1R using small interfering RNA (siRNA) in human prostate and lung cancer cell lines had profound effect on proliferation, clonogenic capability and tumor-sphere formation, indicating reversal of the tumorigenic and stem-like phenotype in absence of Sig1R. Next, in the attempt to discover pharmacological agents that could phenocopy the effects of the genetic knockdown in cancer cells we tested a series of structurally diverse Sig1R ligands selected for high affinity and selectivity for t...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Civenni, G., De Monte, C., Sereni, F., Allegrini, S., Bosotti, R., Laurini, E., Wunsch, B., Pricl, S., Carbone, G. M., Catapano, C. V. Tags: New Molecular Targets: Poster Presentations - Proffered Abstracts Source Type: research
Abstract C131: 'KRAS addiction an artifact of 2D culture? Inhibitors of the mut-KRAS NSCLC 3D growth
Conclusion: Variable enhanced growth dependence on mut-KRAS ("addiction") is seen in 2D but not 3D. Potent and specific inhibition of mut-KRAS cell line growth by CNK1 PH-domain inhibitors is considerably more robust in 3D culture suggesting a novel approach to inhibit mut-KRAS effect on cancer growth.Citation Format: D. Lynn Kirkpatrick, Roisin Delaney, Geoff Grandjean, Assael Madrigal, Martin Indarte, Mike Scott, Garth Powis. ‘KRAS addiction’ an artifact of 2D culture? Inhibitors of the mut-KRAS NSCLC 3D growth. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and ...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Kirkpatrick, D. L., Delaney, R., Grandjean, G., Madrigal, A., Indarte, M., Scott, M., Powis, G. Tags: New Molecular Targets: Poster Presentations - Proffered Abstracts Source Type: research
Abstract C138: Targeting macropinocytosis in pancreatic cancer
In this study, we investigated the effects of knockdown of these three genes on the macropinocytic activity of pancreatic cancer cells. The goal of this study is to assess whether PAK1, ARF6, or SNX5 may serve as potential targets for the suppression of macropinocytosis in pancreatic cancer, which would hamper the cells' uptake of nutrients thus starving the cancer cells and hindering tumor growth. We carried out this study using MIA PaCa-2 pancreatic cancer cells, which are known to exhibit relatively high levels of macropinocytosis. Treatment of cells with siRNA sequences specific to the three genes resulted in a signifi...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Hunt, J., Ng, S., Whatcott, C., Von Hoff, D. D., Han, H. Tags: New Molecular Targets: Poster Presentations - Proffered Abstracts Source Type: research
Abstract C145: Targeted radiosensitization of non-small cell lung cancer (NSCLC) through ADAM17 inhibition
Conclusions: These findings implicate that radiotherapy significantly activates ADAM17 in non–small cell lung cancer (NSCLC) cells, which results in shedding of multiple survival factors, growth factor pathway activation and contributes to treatment resistance. We provide a sound rationale for repositioning ADAM17 inhibitors as short-term adjuvants to improve the radiotherapy outcome of NSCLC.Citation Format: Ashish Sharma, Sabine Bender, Oliver Riesterer, Angela Broggini-Tenzer, Martin Pruschy. Targeted radiosensitization of non-small cell lung cancer (NSCLC) through ADAM17 inhibition. [abstract]. In: Proceedings of...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Sharma, A., Bender, S., Riesterer, O., Broggini-Tenzer, A., Pruschy, M. Tags: Radiotherapeutics: Poster Presentations - Proffered Abstracts Source Type: research
Abstract C150: High expression of SNAI2 is associated with the emergence of a highly motile fulvestrant-resistant phenotype and is an indicator of poor response to endocrine treatment in estrogen receptor-positive metastatic breast cancer
Endocrine resistance is a major clinical problem and is associated with the acquisition of aggressive tumor spread and invasion. To investigate the association between endocrine resistance and tumor cell migration and invasion, we evaluated a panel of MCF7-based cell line models resistant to either tamoxifen, aromatase inhibitors or fulvestrant. Fulvestrant-resistant cell lines showed a significantly higher migration capacity than the parental fulvestrant-sensitive cell line. Gene expression profiling and data analysis using Ingenuity Pathway Analysis (IPA) of these fulvestrant-resistant/fulvestrant-sensitive cell lines id...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Alves, C. L., Elias, D., Lyng, M., Bak, M., Lykkesfeldt, A. E., Ditzel, H. J. Tags: Target Identification and Validation: Poster Presentations - Proffered Abstracts Source Type: research
Abstract A155: Small molecule metabolic inhibitors, compound A and the derivatives specifically inhibit the cell growth of Ewing's sarcoma cells harbor EWS-FLI1 in vitro and in vivo
Conclusions: Compound A and its derivatives may be a therapeutic agent with potent antitumor activity for Ewing's sarcoma patients.Citation Format: Hiromichi Kosaka, Yasuo Watanabe, Michihiro Maemoto, Masamori Sugawara, Miwa Watanabe, Yoko Ono, Yoshisuke Nakasato, Masahiro Matsubara, Ryuichiro Nakai. Small molecule metabolic inhibitors, compound A and the derivatives specifically inhibit the cell growth of Ewing's sarcoma cells harbor EWS-FLI1 in vitro and in vivo. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (P...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Kosaka, H., Watanabe, Y., Maemoto, M., Sugawara, M., Watanabe, M., Ono, Y., Nakasato, Y., Matsubara, M., Nakai, R. Tags: Therapeutic Agents: Other: Poster Presentations - Proffered Abstracts 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 C156: GPCRs as potential therapeutic targets in pancreatic cancer-associated fibroblasts
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense fibrotic stromal matrix, composed of activated fibroblasts (PFs)/stellate cells (PSCs), immune/inflammatory cells and other cell types. This unique tumor microenvironment is increasingly recognized as a key mediator of PDAC progression and drug resistance. Targeting the tumor stroma may thus be a therapeutic approach for PDAC. Pancreatic cancer-associated fibroblasts (CAFs), myofibroblast-like cells that produce extracellular matrix proteins, are responsible for the desmoplasia in PDAC. PSCs and PFs are the key progenitors of CAFs. Blocking the activity of...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Zhou, S., Chang, S., McCann, T., French, R., Lowy, A. M., Insel, P. A. Tags: Target Identification and Validation: Poster Presentations - Proffered Abstracts Source Type: research
Abstract A164: The small molecule UAE inhibitor TAK-243 (MLN7243) prevents DNA damage repair and reduces cell viability/tumor growth when combined with radiation, carboplatin and docetaxel
Clinical results of VELCADE® (bortezomib) For Injection have prompted evaluation of other enzymes within the ubiquitin proteasome system (UPS) as druggable targets for human cancer. We have identified a first in class investigational drug, TAK-243 (MLN7243), which targets the ubiquitin activating enzyme, UAE (UBA1), an essential cellular enzyme responsible for activating > 99% of all cellular ubiquitin. Ubiquitin is involved in multiple cellular processes including ubiquitin-dependent protein turnover, cell cycle progression, regulation of apoptosis, protein localization and response to DNA damage. Experiments combi...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Milhollen, M. A., Shi, J., Traore, T., Huck, J., Sappal, D., Duffy, J., Lightcap, E., Ishii, Y., Ciavarri, J., Fleming, P., Bence, N., Hyer, M. L. Tags: Therapeutic Agents: Other: Poster Presentations - Proffered Abstracts Source Type: research
Abstract B164: Identification and validation of PRMT1 as a therapeutic target in breast cancer
Triple-negative breast cancer (TNBC) represents a subgroup of breast cancers (BC) associated with the most aggressive clinical behavior. No targeted therapy is currently available for the treatment of patients with TNBC. In the present study, we found that Protein Arginine Methyltransferase 1 (PRMT1) is overexpressed in TNBC at the mRNA level. At the protein level, PRMT1 was overexpressed in all breast cancer subtypes compared to normal breast tissue. The depletion of PRMT1 using siRNA in BC cell lines triggered apoptosis, reduced cell viability and the ability to form colonies in an anchorage-independent manner. Treatment...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Silvestre, D. C., Brisson, A., Marty-Prouvost, B., Gentien, D., Loew, D., Dingli, F., Maire, V., Nemati, F., Ye, M., Meseure, D., Nicolas, A., Roman-Roman, S., Dubois, T. Tags: Target Identification and Validation: Poster Presentations - Proffered Abstracts Source Type: research
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 A103: Cell-autonomous activation of the interferon/STAT1 pathway in response to genotoxic treatment
In conclusion, this study supports that cell-autonomous activation of the IFN/STAT1 pathway is a surrogate biomarker of initial tumor shrinkage in response to genotoxics, and suggests that it may play a role in tumor resistance to treatment.Citation Format: Julie Gaston, Laura Cheradame, Marie-Emmanuelle Legrier, Olivier Déas, Myriam Lassalle, Enora Le Ven, Jean-Gabriel Judde, Vincent Goffin, Stefano Cairo. Cell-autonomous activation of the interferon/STAT1 pathway in response to genotoxic treatment. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Gaston, J., Cheradame, L., Legrier, M.-E., Deas, O., Lassalle, M., Le Ven, E., Judde, J.-G., Goffin, V., Cairo, S. Tags: In Vitro and in Vivo Models for Targets: 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
