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Cancer: HER2

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Total 260 results found since Jan 2013.

Abstract 3908: Focal adhesion kinase (FAK) inhibitor VS-6063 (defactinib) preferentially targets cancer stem cells in triple negative breast cancer
We report here that VS-6063 preferentially targets CSCs in preclinical models of TNBC. The effect of VS-6063 on CSCs was assessed in a panel of orthogonal assays. Treatment of human TNBC cells with VS-6063 in 3D matrigel reduced the percentage of Aldefluor+ CSCs, Hoechst dye-excluding side population (SP) CSCs, and tumorsphere-forming efficiency in a serial tumorsphere passaging assay, suggesting that VS-6063 preferentially inhibits CSCs. VS-6063 also reduced the proportion of Aldefluor+ CSCs in primary breast cancer tissue specimens cultured ex vivo. Consistent with the concept that the effect of VS-6063 on CSCs is mediat...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Xu, Q., Kolev, V. N., Wright, Q. G., Ring, J. E., Vidal, C. M., Shapiro, I. M., Weaver, D. T., Padval, M. V., Pachter, J. A. Tags: Tumor Biology Source Type: research

Abstract 3653: Nanoparticle-delivered T7-synthesized siRNA enhances cell killing in HER-2 (+) breast cancer
In this study, a modified siRNA capable of both gene silencing and immunostimulation is the payload. Here, we test the hypothesis that ligand-directed, protein-based nanoparticles delivering siRNA launch a three-pronged attack on tumors by combining missile-like targeting (known as “transductional targeting”) with siRNA-mediated gene silencing, and cytokine-mediated cell death. The latter effect will be accomplished by taking advantage of the normally undesirable cytokine-mediated cytotoxicity induced by epigenetic modifications on certain forms of siRNA, and delivering this to tumors. Here we will deliver siRNA produc...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Alonso-Valenteen, F., , M.-K. Tags: Immunology Source Type: research

Abstract 4381: MiR-205 and Trastuzumab: Potential as adjuvant therapeutic tool and predictive biomarker
Despite the improvement in the management of HER2+ breast cancer patients with the approval of Trastuzumab in the clinical practise, and the success rate of this treatment, a still considerable percentage of patients do not respond or eventually develop a secondary resistance, leading to relapse and poor outcome. A crucial issue is represented by the urgent need of biomarkers able to predict the response to treatment, and certainly of new therapeutic tools to counteract the resistance mechanisms. It is known that resistance to anti-HER2 therapies can be due to escape mechanisms triggered by alternative receptors: here we s...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: D'Ippolito, E., Piovan, C., Plantamura, I., Giussani, M., Casalini, P., Campiglio, M., Tagliabue, E., Iorio, M. V. Tags: Molecular and Cellular Biology Source Type: research

Abstract 3165: Docosahexaenoic acid attenuates survival and progression in subtype-specific breast cancer by modifying Myc activity
Overexpression of Myc in breast cancer is associated with poor prognosis and has a unique profile distribution among subtypes. Myc overexpression has been shown to be greatest in basal-like tumors, ∼50%, and least in luminal Her2-overexpressing tumors, ∼9%. Previous studies from our laboratory have identified a relationship between docosahexaenoic acid (DHA, C22:6 n-3) treatment and Myc activity and the effect seems to be specific to the breast cancer subtype and Myc overexpression profile, but is still unclear. In the current study, we investigated the effect of DHA on tumor growth, survival, and invasion in a high My...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Mouradian, M., Bains, P. K., Chattin, A. M., Pardini, R. S. Tags: Tumor Biology Source Type: research

Abstract 5416: Development of a nanoparticle platform for the targeted delivery of siRNA to HER2-positive breast cancers
Successful siRNA based therapy has the potential to revolutionize cancer therapy by mediating the silencing of any gene deemed important for disease progression. However, unprotected siRNA has a short half-life in blood and lacks the ability to selectively identify target cells. Our group is developing an effective siRNA based nanoparticle platform that overcomes these shortcomings by utilizing a mesoporous silica nanoparticle electrostatically loaded with siRNA and conjugated with an antibody for target homing. The human epidermal growth receptor type 2 (HER2) is a highly validated therapeutic target in breast cancer due ...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Goodyear, S. M. Tags: Cancer Chemistry Source Type: research

Abstract SY43-03: Screening for triple negative breast cancer vulnerabilities
There is no targeted therapy for triple negative breast cancers (TNBC), which have the worst prognosis of human breast cancers. TNBCs are prone to relapse and metastasize after cytotoxic drug treatment. This group of cancers, defined by low or absent expression of estrogen, progesterone and Her2 receptors, are heterogeneous in genetic, epigenetic and phenotypic features, making it difficult to identify specific drug targets suitable for this group of cancers as a whole. About half or more of TNBCs have an epithelial phenotype (classified based on gene expression profiling as basal-like or basal-A) and a large minority of t...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Petrocca, F., Altschuler, G., Tan, S. M., Mendillo, M. L., Yan, H., Jerry, D. J., Kung, A. L., Hide, W., Ince, T. A., Lieberman, J. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 5449A: PI3K and MEK inhibition in intracranial triple negative breast cancer: Efficacy of BKM120 and AZD6244 in preclinical mouse models
Conclusions: BKM120 and AZD6244 both improved survival in an IC TNBC SUM149 mouse model, with single agent AZD6244 being most efficacious. The siRNA screens indicate that combined treatment with BKM120 and AZD6244 should be synthetically lethal, suggesting that combination therapy may have underperformed due to toxicity. Ongoing in vitro and in vivo studies (including dosing schedules) will further characterize the effects of these drugs in intracranial TNBC. Citation Format: Amanda E.D. Van Swearingen, Marni B. Siegel, Ryan Bash, Brian Golitz, Charlene Santos, David Darr, Joel Parker, Gary L. Johnson, C. Ryan Miller, Care...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Swearingen, A. E. D. V., Siegel, M. B., Bash, R., Golitz, B., Santos, C., Darr, D., Parker, J., Johnson, G. L., Miller, C. R., Anders, C. K. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 3783: Adipocytes inhibit trastuzumab-mediated ADCC via induction of GDF15
Conclusion: Adipocytes inhibit antitumor activity of trastuzumab in HER2-expressing breast cancer cells via secretion of factors that reduce cancer cell sensitivity to ADCC. Our findings underline the importance of adipose tissue in the resistance to trastuzumab, and suggest that development of approaches targeting GDF15 may sensitize cancer cells to trastuzumab-based therapy. Citation Format: Minh Ngoc Duong, Aurore Cleret, Eva-Laure Matera, Kamel Chettab, Doriane Poloni, Sandrine Valsesia-Wittmann, Béatrice Clémenceau, Charles Dumontet. Adipocytes inhibit trastuzumab-mediated ADCC via induction of GDF15. [abstract]. In...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Duong, M. N., Cleret, A., Matera, E.–L., Chettab, K., Poloni, D., Valsesia–Wittmann, S., Clemenceau, B., Dumontet, C. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 3029: MKP1-mediated survival of HER2 positive breast cancer stem cells
The overall cure rate of primary tumors has been significantly improved in the last three decades; however, metastatic and recurrent tumors with aggressive growth and therapy-resistance remain as the major factors shortening breast cancer patients’ survival. MKP1, a mitogen-activated protein kinase (MAPK) phosphatase, was shown to be linked with chemoresistance in breast cancer cells and was over-expressed in radio-resistant breast cancer cells that survived long-term fractionated irradiation. Herein, we showed that MKP1 is expressed exclusively in HER2 positive clinical breast tumors compared to HER2 negative tumors. Co...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Candas, D., Lu, C.-L., Fan, M., Chuang, F., Sweeney, C., Borowsky, A., Li, J. J. Tags: Tumor Biology Source Type: research

Abstract 3294: Notch signaling is regulated by vacuolar ATPase in triple negative breast cancer
Triple Negative Breast Cancer (TNBC) constitutes 15 % of all diagnosed breast cancers. It is more common among African American and younger women. TNBC cells do not express Estrogen, Progesterone and Her2 receptors. As a result, patients have limited treatment options. To effectively treat TNBC, it is important to identify and target specific signaling pathways that contribute to TNBC tumorigenesis. Notch signaling is an evolutionarily conserved juxtacrine pathway that is important in normal mammary development and has been shown to play a role in TNBC progression. Although there has been considerable research on role of N...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Pamarthy, S., Beaman, K. D. Tags: Molecular and Cellular Biology Source Type: research

Abstract 3299: Maternal embryonic leucine zipper kinase is critical for the growth and migration of triple negative breast cancer cells
Conclusions: MELK is an important growth regulator of TNBC, but not of ER positive breast cancers. Our results indicate that MELK promotes cell migration in TNBC cells. These findings suggest that MELK is a promising target for the treatment of TNBC. Supported by a Susan G. Komen for the Cure Promise Grant (KG081694), and the John Charles Cain Award. Citation Format: Nidhi Batra, Corey Speers, Ivan Uray, Abhijit Mazumdar, Anna Tsimelzon, Susan Hilsenbeck, Gordon Mills, Powel Brown. Maternal embryonic leucine zipper kinase is critical for the growth and migration of triple negative breast cancer cells. [abstract]. In: Proce...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Batra, N., Speers, C., Uray, I., Mazumdar, A., Tsimelzon, A., Hilsenbeck, S., Mills, G., Brown, P. Tags: Molecular and Cellular Biology Source Type: research

Abstract 5469: Trastuzumab resistant HER2+ breast cancer cells retain sensitivity to poly (ADP-ribose) polymerase (PARP) inhibition
Conclusions: HER2+ breast cancer cells resistant to trastuzumab continue to be sensitive to PARP inhibition through attenuation of the NF-κB signaling pathway. These results support the use of PARPi as part of a therapeutic strategy for patients with HER2+ breast cancer. Citation Format: Monica E. Wielgos, Tiffiny Cooper, Andres Forero, James A. Bonner, Francisco J. Esteva, C K. Osborne, Rachel Schiff, Albert F. LoBuglio, Eddy S. Yang. Trastuzumab resistant HER2+ breast cancer cells retain sensitivity to poly (ADP-ribose) polymerase (PARP) inhibition. [abstract]. In: Proceedings of the 105th Annual Meeting of the American...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Wielgos, M. E., Cooper, T., Forero, A., Bonner, J. A., Esteva, F. J., Osborne, C. K., Schiff, R., LoBuglio, A. F., Yang, E. S. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 3334: The role of nuclear HER3 in breast cancer resistance
HER3 is reported to be overexpressed in 18-29% of human breast cancers and suggested to be a marker of reduced disease-specific survival in 4,406 patients with invasive breast carcinoma. Overexpression and subcellular localization of HER3 may be a negative predictive marker for targeted therapies, and HER3 status may play a role in the development of drug resistance and metastasis. Translocation of ERBB family members EGFR, HER2 and HER4 into nucleus for regulating gene transcription have been reported, but only a few studies about nuclear HER3 have been reported and the biological role of nuclear HER3 is still unknown. HE...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Tang, P. M. K., Khoo, U. S., Harris, A. L., Kong, A. Tags: Molecular and Cellular Biology Source Type: research

Essential role of the cancer stem/progenitor cell marker nucleostemin for indole-3-carbinol anti-proliferative responsiveness in human breast cancer cells
Conclusions: Our results provide the first evidence that a natural anti-cancer compound mediates its cellular and in vivo tumor anti-proliferative responses by selectively stimulating cellular interactions of the stem/progenitor cell marker nucleostemin with MDM2, which frees p53 to trigger its apoptotic response. Furthermore, our study provides a new mechanistic template that can be potentially exploited for the development of cancer stem/progenitor cell targeted therapeutic strategies.
Source: BMC Biology - Latest articles - September 12, 2014 Category: Biology Authors: Antony TinAnna ParkShyam SundarGary Firestone Source Type: research

Profiling the tyrosine phosphoproteome of different mouse mammary tumour models reveals distinct, model-specific signaling networks and conserved oncogenic pathways
Conclusion: This study provides network-level insights into signaling in these breast cancer models and demonstrates that comparative phosphoproteomics can identify conserved oncogenic signaling pathways. The Met-amplified, p53-null tumours provide a new pre-clinical model for a subset of triple-negative breast cancers.
Source: Breast Cancer Research - September 9, 2014 Category: Cancer & Oncology Authors: Naveid AliJianmin WuFalko HochgräfeHoward ChanRadhika NairSunny YeLuxi ZhangRuth LyonsMark PineseHong LeeNicola ArmstrongChristopher OrmandySusan ClarkAlexander SwarbrickRoger Daly Source Type: research