Atu027, a Liposomal Small Interfering RNA Formulation Targeting Protein Kinase N3, Inhibits Cancer Progression

Aleku, Manuela; Schulz, Petra; Keil, Oliver; Santel, Ansgar; Schaeper, Ute; Dieckhoff, Britta; Janke, Oliver; Endruschat, Jens; Durieux, Birgit; Röder, Nadine; Löffler, Kathrin; Lange, Christian; Fechtner, Melanie; Möpert, Kristin; Fisch, Gerald; Dames, Sibylle; Arnold, W; Jochims, Karin; Giese, Klaus; Wiedenmann, Bertram; Scholz, Arne; Kaufmann, Jörg

doi:10.1158/0008-5472.can-08-2428

Cited by 278 publications

(184 citation statements)

References 48 publications

Supporting

Mentioning

175

Contrasting

Unclassified

Order By: Relevance

“…With respect to immunoliposomes, although many preclinical studies can be found in the literature [24,215,275,276] and a few clinical trials are in progress [18,75,[277][278][279] an siRNA that targets PKN3 [18,286], or TKM-PLK1 that includes siRNA against PLK1 for the treatment of neuroendocrine tumors and adrenocortical carcinomas (phase I/II clinical trials) [283,287,288]. The phase I liposomic formulation SGT-53 includes plasmidic DNA that expresses the tumor suppressor gene p53 to treat solid tumors [280,289].…”

Section: Nl Cpt-11mentioning

confidence: 99%

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Pérez-Herrero

Fernández‐Medarde

2015

European Journal of Pharmaceutics and Biopharmaceutics

1,460

754

View full text Add to dashboard Cite

Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vasculatization and, in time, adquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastasic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, like the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic Código de campo cambiado

show abstract

Section: Nl Cpt-11mentioning

confidence: 99%

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Pérez-Herrero

Fernández‐Medarde

2015

European Journal of Pharmaceutics and Biopharmaceutics

1,460

754

View full text Add to dashboard Cite

show abstract

“…However, delivering siRNA to tumors using clinically acceptable delivery strategies remains a major technical hurdle (2,3). Over the last 10 years, various proof-of-concept successes of in vivo siRNA delivery to tumors have been reported using delivery vehicles such as liposomes, cationic polymers, and other materials (4)(5)(6)(7)(8)(9)(10). To select the most promising delivery platform for the development of siRNA therapeutics, we evaluated the majority of available delivery technologies for their abilities to deliver siRNA into tumors using the previously described positive-readout tumor models (11).…”

Section: Introductionmentioning

confidence: 99%

Developing Lipid Nanoparticle-Based siRNA Therapeutics for Hepatocellular Carcinoma Using an Integrated Approach

Wang

Wilcox

et al. 2013

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Successful siRNA therapeutics requires the optimal integration of multiple components, including an efficient delivery system, a disease indication that is appropriate for siRNA-based therapy, and a potent and nontoxic siRNA against a robust therapeutic target. Although all currently available delivery systems have limitations, it is important to recognize that a careful selection of the disease indication, therapeutic target, and siRNA molecule could partially compensate for deficiencies associated with the delivery system and makes it possible to advance a therapeutic siRNA regimen. In this study, we present the development of siRNA therapeutics for hepatocellular carcinoma using an integrated approach, including the development of an efficient lipid nanoparticle delivery system, the identification of a robust therapeutic target that does not trigger liver toxicity upon target knockdown, and the selection of potent and nonimmunogenic siRNA molecules against the target. The resulting siRNA-containing lipid nanoparticles produced significant antitumor efficacy in orthotopic hepatocellular carcinoma models, and, thus, represent a promising starting point for the development of siRNA therapeutics for hepatocellular carcinoma.

show abstract

“…However, siRNA administered through this route can be easily degraded. 19 In many cases, siRNA induces the silencing of unintended genes (off-target effects) because of sequence similarity between the mRNAs of the target and nontarget genes. 20 Furthermore, siRNA readily induces immune responses in vivo.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Efp by DNA-modified small interfering RNA inhibits breast cancer cell proliferation and in vivo tumor growth

et al. 2010

View full text Add to dashboard Cite

The estrogen-responsive gene Efp promotes the growth of breast cancer cells by stimulating the degradation of a negative cell-cycle regulator, 14-3-3s, and is hence considered a suitable molecular target for breast cancer therapy. The use of small interfering RNA (siRNA) and its derivatives to silence cancer-related genes is being investigated with the aim of identifying clinical applications for these molecules. Recently, it has been shown that DNA-modified siRNA (chimeric siRNA) has good potential in clinical applications, because it induces fewer off-target effects or immune responses in mammalian cells. In the present study, we identified the most specific and effective siRNA (siEfp-1) for silencing Efp expression in MCF-7 breast cancer cells. For this purpose, we used an algorithm that primarily eliminates off-target effects. siEfp-1 considerably suppressed the in vitro proliferation and cell-cycle progression of MCF-7 cells, as well as the in vivo growth of MCF-7 tumors, in athymic mice. DNA-modified siEfp-1 (chimeric siEfp) significantly inhibited the expression of Efp, proliferation of cultured cells and the in vivo growth of MCF-7-derived tumors in athymic mice. In addition, the silencing of Efp expression by siEfp-1 and chimeric siEfp increased the expression of the 14-3-3s protein. These results suggest that siEfp-1 and chimeric siEfp could be useful in breast cancer therapy. Chimeric siEfp, in particular, has a high specificity and induces few side effects and is therefore expected to be used as a novel nucleic acid-based therapeutic agent.

show abstract

Atu027, a Liposomal Small Interfering RNA Formulation Targeting Protein Kinase N3, Inhibits Cancer Progression

Cited by 278 publications

References 48 publications

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Developing Lipid Nanoparticle-Based siRNA Therapeutics for Hepatocellular Carcinoma Using an Integrated Approach

Knockdown of Efp by DNA-modified small interfering RNA inhibits breast cancer cell proliferation and in vivo tumor growth

Contact Info

Product

Resources

About