RNA Interference for Cancer Therapy

Cheng, Kun; Qin, Bin

doi:10.1007/978-1-4419-0131-6_13

Cited by 6 publications

(5 citation statements)

References 155 publications

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“…[116] Potent knockdown of specific gene sequence makes siRNA a promising therapeutic approach for cancer therapy. [31, 117] Inhibition of HER2 expression by a retrovirus-mediated shRNA (short hairpin RNA) resulted in cell cycle arrest at G 0 /G 1 , increased apoptosis, reduced proliferation, and growth inhibition in breast and ovarian tumor cells overespressing HER2.…”

Section: Her2 As a Target For Cancer Therapymentioning

confidence: 99%

The role of HER2 in cancer therapy and targeted drug delivery

Tai

Mahato

Cheng

2010

Journal of Controlled Release

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465

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HER2 is highly expressed in a significant proportion of breast cancer, ovarian cancer, and gastric cancer. Since the discovery of its role in tumorigenesis, HER2 has received great attention in cancer research during the past two decades. Successful development of the humanized monoclonal anti-HER2 antibody (Trastuzumab) for the treatment of breast cancer further spurred scientists to develop various HER2 specific antibodies, dimerization inhibitors and kinase inhibitors for cancer therapy. On the other hand, the high expression of HER2 and the accessibility of its extracellular domain make HER2 an ideal target for the targeted delivery of anti-tumor drugs as well as imaging agents. Although there is no natural ligand for HER2, various artificial ligands targeting HER2 have been developed and applied in various targeted drug delivery systems. The emphasis of this review is to elucidate the roles of HER2 in cancer therapy and targeted drug delivery. The structure and signal pathway of HER2 will be briefly described. The role of HER2 in tumorigenesis and its relationship with other tumor markers will be discussed. For the HER2 targeted cancer therapy, numerous strategies including the blockage of receptor dimerization, inhibition of the tyrosine kinase activity, and interruption of the downstream signal pathway will be summarized. For the targeted drug delivery to HER2 positive tumor cells, various targeting ligands and their delivery systems will be described in details.

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Section: Her2 As a Target For Cancer Therapymentioning

confidence: 99%

The role of HER2 in cancer therapy and targeted drug delivery

Tai

Mahato

Cheng

2010

Journal of Controlled Release

Self Cite

465

330

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“…4, 5 To exert its therapeutic action, siRNA needs to overcome a number of biological barriers before it can enter cell cytoplasm. 6–8 Non-viral delivery systems, such as bio-conjugates, liposomes, cationic peptides/polymers, and several other types of nanoparticles have been extensively investigated because of their safety. 9–11 …”

Section: Introductionmentioning

confidence: 99%

Intracellular trafficking and exocytosis of a multi-component siRNA nanocomplex

Shukla

Jain

Zhao

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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Despite the importance of siRNA delivery systems, understanding of their intracellular fate remains elusive. We recently developed a multi-component siRNA nanocomplex to deliver siRNA to hepatic stellate cells (HSCs). The objective of this study is to study post internalization trafficking of this siRNA nanocomplex and its multiple components like siRNA, protamine, and streptavidin, in HSCs. After internalization, the nanocomplex entrapped in early endosomes undergoes three possible routes including endosomal escape, exocytosis, and entrapment in lysosomes. Significant amount of siRNA dissociates form the nanocomplex to exert silencing activity. After escaping from endosomes, protamine dissociates from the nanocomplex and stays inside the cytoplasm. Golgi complex plays an important role in exocytosis of the nanocomplex. We also demonstrate that exocytosis is one of the major reasons accounting for the transient silencing activity of nonviral siRNA delivery. Incorporation of exocytosis inhibitors in nonviral siRNA delivery systems may extend the silencing activity of siRNA.

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“…Among various strategies to inhibit a gene expression, small interference RNA (siRNA) represents a considerable promise for cancer therapy due to its potent and specific knockdown effect (15,16). In the present study, we intend to silence the IKKα expression in prostate cancer cells using synthetic siRNA and evaluate its effects on tumor cell invasiveness and growth.…”

Section: Introductionmentioning

confidence: 99%

Blocking IKKα Expression Inhibits Prostate Cancer Invasiveness

2010

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Purpose IKKα has been recently identified as a key mediator of the inflammation and metastasis in prostate cancer. In the present study, we intend to silence the IKKα expression in prostate cancer cells using synthetic siRNAs and examine their biological effects on tumor cell invasiveness and growth. Methods Three synthetic siRNAs targeting different regions of the IKKα mRNA were designed, and the silencing effect was determined in PC-3 and DU145 cells. Numerous studies, including wound-healing assay, migration assay, invasion assay, cell attachment assay, cell proliferation, and cell cycle analysis, were conducted to investigate the biological effects of the IKKα siRNAs on prostate cancer cells. Results We have identified potent siRNAs that can silence the IKKα up to 74%. Inhibition of IKKα reduced the wound healing, migration, invasion and cell attachment capabilities of prostate cancer cells. Similar anti-invasive effects were also observed in the presence of RANKL. However, silencing of IKKα only showed a negligible effect on cell proliferation and cell cycle distribution. Conclusion This study presents compelling evidence that IKKα plays a major role in prostate cancer invasion and metastasis, but not in cell proliferation. Silencing of IKKα with siRNA may therefore provide a promising therapeutic strategy for prostate cancer patients.

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RNA Interference for Cancer Therapy

Cited by 6 publications

References 155 publications

The role of HER2 in cancer therapy and targeted drug delivery

The role of HER2 in cancer therapy and targeted drug delivery

Intracellular trafficking and exocytosis of a multi-component siRNA nanocomplex

Blocking IKKα Expression Inhibits Prostate Cancer Invasiveness

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