Selective Raf inhibition in cancer therapy

Khazak, Vladimir; Astsaturov, Igor; Serebriiskii, Ilya G.; Golemis, Erica A.

doi:10.1517/14728222.11.12.1587

Cited by 71 publications

(51 citation statements)

References 187 publications

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“…Small inhibitory molecules such as asDNA, siRNA, and antibodies have been developed to target the mitogen-activated protein kinase pathway (29). Recently, it has been described that miR-125b, which is downregulated in breast cancer cells, targets the mRNA of erbB2 (3).…”

Section: Introductionmentioning

confidence: 99%

A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

Hofmann

Heinrich

Radziwil

et al. 2009

Molecular Cancer Research

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The noncoding RNA miR-125b has been described to reduce ErbB2 protein expression as well as proliferation and migration of cancer cell lines. As additional target of miR-125b, we identified the c-raf-1 mRNA by sequence analysis. We designed a short hairpin-looped oligodeoxynucleotide (ODN) targeted to the same 3′ untranslated region of c-raf-1 mRNA as miR-125b. The fully complementary ODN antisense strand is linked to a second strand constituting a partially double-stranded structure of the ODN. Transfection of the c-raf-1-specific ODN (ODN-Raf) in a breast cancer cell line reduced the protein levels of C-Raf, ErbB2, and their downstream effector cyclin D1 similar to miR-125b. MiR-125b as well as ODN-Raf showed no effect on the c-raf-1 mRNA level in contrast to small interfering RNA. Unlike miR-125b, ODN-Raf induced a cytopathic effect. This may be explained by the structural properties of ODN-Raf, which can form G-tetrads. Thus, the short hairpin-looped ODN-Raf, targeting the same region of c-raf-1 as miR-125b, is a multifunctional molecule reducing the expression of oncoproteins and stimulating cell death. Both features may be useful to interfere with tumor growth. (Mol Cancer Res 2009;7(10):1635-44)

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Section: Introductionmentioning

confidence: 99%

A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

Hofmann

Heinrich

Radziwil

et al. 2009

Molecular Cancer Research

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“…S6). Furthermore, we evaluated if RAF activities are required for sustained activation of MEK/ERK signaling in A375-R1 cells by using RAF265, a small molecule inhibitor of pan-RAF (34,35). RAF265 inhibited the proliferation of the parental A375 and A375-R1 cells with similar potencies with IC 50 values of 458 nM and 235 nM, respectively (Fig.…”

Section: Mek/erk Signaling Is Reactivated and Resistant To B-raf Inhimentioning

confidence: 99%

Reactivation of Mitogen-activated Protein Kinase (MAPK) Pathway by FGF Receptor 3 (FGFR3)/Ras Mediates Resistance to Vemurafenib in Human B-RAF V600E Mutant Melanoma

Yadav

Zhang

Liu

et al. 2012

Journal of Biological Chemistry

177

144

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Background: B-RAF V600E melanomas rapidly develop resistance to B-RAF inhibitors in the clinic. Results: FGFR3/Ras signaling is elevated and induces resistance to vemurafenib in vemurafenib-resistant cells. Conclusion: FGFR3/Ras confers resistance to B-RAF inhibition via MAPK pathway reactivation. Significance: A novel mechanism of resistance to B-RAF inhibitors is described and potential therapeutic strategies are suggested.

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“…Antisense oligonucleotide that had anti-tumor-growth effects in breast, lung, and ovarian cancer mouse xenograft models [132] LErafAON A liposome-entrapped antisense oligodeoxyribonucleotide. Patients with advanced solid tumor showed reduced mRNA and protein levels of c-Raf-1 [134] RASSF1A 5-aza-2-deoxycytidine (AZA) and trichostatin A (TSA)…”

Section: Lats2mentioning

confidence: 99%