Clinical aspects for survivin: a crucial molecule for targeting drug-resistant cancers

Singh, Neha; Krishnakumar, Subramanian; Kanwar, Rupinder K.; Cheung, Chun Hei Antonio; Kanwar, Jagat R.

doi:10.1016/j.drudis.2014.11.013

Cited by 75 publications

(70 citation statements)

References 84 publications

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“…Survivin carries out its antiapoptotic function through inhibition of caspase-9, for which the presence of a helper protein, hepatitis B X-interacting protein (HBXIP), is necessary [24], and thus plays an important role in cancer drug resistance. As a consequence, survivin is a very promising biomarker for drug resistance [43]. Survivin dysregulation in human cancers can be the result of epigenetic mechanisms due to promoter methylation [44].…”

Section: Discussionmentioning

confidence: 99%

miR-218 targets survivin and regulates resistance to chemotherapeutics in breast cancer

Yagüe

2015

Breast Cancer Res Treat

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Multidrug resistance (MDR) remains one of the most significant obstacles in breast cancer treatment, and this process often involves dysregulation of a great number of microRNAs (miRNAs). Some miRNAs are indicators of drug resistance and confer resistance to chemotherapeutic drugs, although our understanding of this complex process is still incomplete. We have used a combination of miRNA profiling and real-time PCR in two drug-resistant derivatives of MCF-7 and Cal51 cells. Experimental modulation of miR expression has been obtained by retroviral transfection. Taxol and doxorubicin IC50 values were obtained by short-term drug sensitivity assays. Apoptosis was determined by flow cytometry after annexin V staining, by caspase 3/7 and caspase 9 activity assays and the levels of apoptosis-related proteins bcl-2 and bax by real-time PCR and Western blot. miR target was studied using transient transfection of luciferase constructs with the 3 untranslated regions (UTR) of target mRNAs. Small interfering RNA-mediated genetic knock-down was performed in MDR cells and its modulatory effect on apoptosis examined. The effect of miRNA on tumorigenicity and tumor drug response was studied in mouse xenografts. miRNA profiling of two drug-resistant breast cancer cell models indicated that miR-218 was down-regulated in both MCF-7/A02 and CALDOX cells. Ectopic expression of miR-218 resensitized both drug-resistant cell lines to doxorubicin and taxol due to an increase in apoptosis. miR-218 binds survivin (BIRC5) mRNA 3-UTR and down-regulated reporter luciferase activity. Experimental down-regulation of survivin by RNA interference in drug-resistant cells did mimic the sensitization observed when miRNA-218 was up-regulated. In addition, resensitization to taxol was also observed in mouse tumor xenografts from cells over-expressing miR-218. miR-218 is involved in the development of MDR in breast cancer cells via targeting survivin and leading to evasion of apoptosis. Targeting miR-218 and survivin may thus provide a potential strategy for reversing drug resistance in breast cancer

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Section: Discussionmentioning

confidence: 99%

miR-218 targets survivin and regulates resistance to chemotherapeutics in breast cancer

Yagüe

2015

Breast Cancer Res Treat

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“…Survivin, a member of the inhibitor of apoptosis proteins (IAP) has been described as a biomarker for chemoresistance in various cancers. The recent studies explain the role of survivin in drug resistance of cancer and propose targeted therapy for survivin for effective chemotherapy [30]. However, the relation of survivin expression to CD133 in colon cancer is not clear yet.…”

Section: Introductionmentioning

confidence: 99%

Chemoresistance of CD133 + colon cancer may be related with increased survivin expression

Lee

Mia-Jan

et al. 2015

Biochemical and Biophysical Research Communications

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“…However, survivin-targeted therapy has only met with limited success in clinical trials, purportedly undermined by inefficient delivery and poor bioavailability of the synthetic inhibitors and/or interfering RNAs [5,7]. Moreover, many normal cell types also express survivin, including vascular endothelial cells (ECs), primitive hematopoietic cells and T lymphocytes [8].…”

Section: Introductionmentioning

confidence: 98%

“…Upregulation of IAP expression has been correlated with drug resistance in several cancers [4]. Survivin (encoded by BIRC5), the smallest member of the IAPs family, has been associated with both the control of cell apoptosis and regulation of cell mitosis in cancer [5]. Owing to its preferential expression in tumor versus normal tissues [6], survivin has long been considered a prime cancer-specific drug target.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle-mediated inhibition of survivin to overcome drug resistance in cancer therapy

Wang

Chan

et al. 2016

Journal of Controlled Release

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Clinical aspects for survivin: a crucial molecule for targeting drug-resistant cancers

Cited by 75 publications

References 84 publications

miR-218 targets survivin and regulates resistance to chemotherapeutics in breast cancer

miR-218 targets survivin and regulates resistance to chemotherapeutics in breast cancer

Chemoresistance of CD133 + colon cancer may be related with increased survivin expression

Nanoparticle-mediated inhibition of survivin to overcome drug resistance in cancer therapy

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