Association of survivin splice variants with prognosis and treatment of breast cancer

Pavlidou, Anastasia; Kroupis, Christos; Dimas, Kostas

doi:10.5306/wjco.v5.i5.883

Cited by 28 publications

(24 citation statements)

References 59 publications

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“…These data strengthen the hypothesis that survivin is a mediator of drug resistance. This is supported by data suggesting that the increase of this protein in cancer tissues is an unfavorable prognostic marker and is associated with increased risk of recurrence (19). The overexpression of survivin has been proposed as a predictive factor in determining the response to chemotherapy (20).…”

Section: Discussionsupporting

confidence: 63%

Resistance to the mTOR inhibitor everolimus is reversed by the downregulation of survivin in breast cancer cells

et al. 2017

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Abstract. Everolimus (RAD001) is an inhibitor of mammalian target of rapamycin used in combination with exemestane to treat hormone receptor-positive advanced breast cancer. However, not all patients are equally sensitive to RAD001 and certain patients develop resistance. Therefore, the present study analyzed the mechanisms involved in the resistance of breast cancer cells to RAD001 in order to identify a potential tool to overcome it. The effects of RAD001 on the inhibition of cell viability, on the induction of apoptosis and autophagy and on the regulation of survivin, an anti-apoptotic protein, were evaluated in two breast cancer cell lines: BT474 (luminal B) and MCF7 (luminal A). RAD001 was demonstrated to induce autophagy in the two cell lines at following a short period of treatment (4 h) and to induce apoptosis exclusively in BT474 cells following longer periods of treatment (48 h). RAD001 induced the downregulation of survivin in BT474 cells and its upregulation in MCF7 cells. Consequently, inhibiting survivin with YM155 resulted in the acquired resistance of MCF7 cells to RAD001 being reverted, restoring RAD001-induced apoptosis. These data demonstrated that RAD001 exerted anti-proliferative and pro-apoptotic effects on breast cancer cells, but that these effects were repressed by the simultaneous up-regulation of survivin. Finally, the results demonstrated that inhibiting the expression of survivin resulted in the restoration of the anti-neoplastic activity of RAD001.

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Section: Discussionsupporting

confidence: 63%

Resistance to the mTOR inhibitor everolimus is reversed by the downregulation of survivin in breast cancer cells

et al. 2017

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“…Survivin is a 142-animo acid peptide that is encoded by Baculoviral IAP Repeat Containing 5 (BIRC5) gene located on chromosome 17 and usually exists in the form of a homodimer [4]. In addition to the full-length wild type (WT) transcript, there are six splice variants, a consequence of alternative splicing, that have been reported [5]. Physiologically, survivin has been shown to play a critical role in apoptosis; however, only the final protein products of the WT survivin, survivin ΔEx3, and survivin 3B transcripts have been confirmed to retain antiapoptotic function [6].…”

Section: Introductionmentioning

confidence: 99%

The role of survivin in the progression of pancreatic ductal adenocarcinoma (PDAC) and a novel survivin-targeted therapeutic for PDAC

et al. 2020

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Treating pancreatic ductal adenocarcinoma (PDAC) remains a major hurdle in the field of oncology. Less than half of patients respond to frontline chemotherapy and the pancreatic tumor microenvironment limits the efficacy of immunotherapeutic approaches. Targeted therapies could serve as effective treatments to enhance the clinical response rate. One potential therapeutic target is survivin, a protein that is normally expressed during embryonic and fetal development and has a critical impact on cell cycle control and apoptosis. In adulthood, survivin is not present in most normal adult cells, but is significantly re-expressed in tumor tissues. In PDAC, elevated survivin expression is correlated with treatment resistance and lower patient survival, although the underlying mechanisms of survivin's action in this type of cancer is poorly understood. Using patient derived xenografts of PDAC and their corresponding primary pancreatic cancer lines (PPCL-46 and PPCL-LM1) possessing increased expression of survivin, we aimed to evaluate the therapeutic response of a novel survivin inhibitor, UFSHR, with respect to survivin expression and the tumorigenic characteristics of PDAC. Cell viability and apoptosis analyses revealed that repressing survivin expression by UFSHR or YM155, a well-known inhibitor of survivin, in PPCLs effectively reduces cell proliferation by inducing apoptosis. Tumor cell migration was also hindered following treatment with YM155 and UFSHR. In addition, both survivin inhibitors, particularly UFSHR, effectively reduced progression of PPCL-46 and PPCL-LM1 tumors, when compared to the untreated cohort. Overall, this study provides solid evidence to support the critical role of survivin in PDAC progression and proposes a novel survivin inhibitor UFSHR that can become an alternative strategy for this type of cancer.

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“…Even though a correlation was identified between nuclear Sur expression and a negative prognosis for breast neoplasia, the study by Lee et al 18 failed to correlate the protein pairing variants with the prognosis. However, this correlation was described in a review of the literature carried out by Pavlidou et al 7 , in which the Sur transcript variants were evaluated according to the clinicopathological characteristics of BC patients and their survival rate.…”

Section: Discussionmentioning

confidence: 99%

“…This antagonist competes with Sur by binding to HSP90 and induces apoptosis through independent and caspase-dependent mechanisms. Regarding anticancer activity, Shepherdin also proved to be highly selective and is, therefore, a potential target for this type of therapy, since its toxicity in normal fibroblasts was found to be low, and no other side effects were observed in normal cells 7,17 .…”

Section: Discussionmentioning

confidence: 99%

The role of Survivin as a biomarker and potential prognostic factor for breast cancer

Veiga

Silva

Pereira

et al. 2019

Rev. Assoc. Med. Bras.

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SUMMARY Breast cancer (BC) is one of the primary health problems worldwide. As the most common cancer in women in the world and in Brasil, behind only non-melanoma skin cancer, this neoplasm corresponds to approximately 28% of new cases per year in the country. BC also affects men, although the incidence corresponds to only 1% of total cases. Currently, most of the chemotherapeutic agents used in BC treatment are extremely toxic and cause long-term side effects. There is also a need to obtain earlier diagnoses, more accurate prognoses and make new therapies available that are more selective and effective in order to improve the current scenario. Therefore, this work sought to evaluate the importance of the biomarker survivin (Sur) in relation to BC, through the detailing of the role of Sur as a biomarker, the correlation between this protein and the prognosis of BC patients, and a summary of therapeutic strategies that target Sur for the development of new anticancer therapies.

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Association of survivin splice variants with prognosis and treatment of breast cancer

Cited by 28 publications

References 59 publications

Resistance to the mTOR inhibitor everolimus is reversed by the downregulation of survivin in breast cancer cells

Resistance to the mTOR inhibitor everolimus is reversed by the downregulation of survivin in breast cancer cells

The role of survivin in the progression of pancreatic ductal adenocarcinoma (PDAC) and a novel survivin-targeted therapeutic for PDAC

The role of Survivin as a biomarker and potential prognostic factor for breast cancer

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