Survivin gene expression and prognosis in recurrent colorectal cancer Reply

Miller, Michal A.

doi:10.1136/gut.48.1.137

Cited by 19 publications

(12 citation statements)

References 4 publications

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“…16,17 Furthermore, the level of survivin expression in tumor tissues is correlated with the prognosis of the patients. 15,18,19 These results have provided the rationale of targeting survivin for cancer therapy. For example, downregulation of survivin expression or function induces apoptotic cell death specifically in tumor cells and enhances the antitumor effects of several chemotherapy drugs.…”

Section: Introductionmentioning

confidence: 99%

Tumor-specific gene expression using the survivin promoter is further increased by hypoxia

Yang

Cao

et al. 2004

Gene Ther

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Increasing evidence indicates that survivin, an inhibitor of apoptosis protein (IAP), is expressed in human cancer cells but is absent from most normal adult tissues. Here, we examined the feasibility of using a survivin promoter (Sur-P) to direct therapeutic expression of a proapoptotic gene specifically in human tumor cells. First, we demonstrated that this promoter was highly active in human tumor cells but not in normal cells. Second, we found that Sur-P activity was upregulated by hypoxia in tumor cells. Third, to further enhance this promoter's activity under hypoxia, we added a hypoxia-responsive element (HRE) from the vascular endothelial growth factor gene promoter in its 5 0 region, and showed that this combination resulted in a further increase in the level of gene expression in hypoxic tumor cells. Finally, we demonstrated that expression of an autocatalytic reverse caspase-3 gene by this promoter specifically induced apoptotic cell death in human tumor cells but not in normal cells. These findings support the use of promoters Sur-P or chimeric HRE-Sur-P for generating novel vectors for cancer gene therapy.

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Section: Introductionmentioning

confidence: 99%

Tumor-specific gene expression using the survivin promoter is further increased by hypoxia

Yang

Cao

et al. 2004

Gene Ther

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“…However, the precise mechanism by which survivin inhibits apoptosis is not very clear. Retrospective analysis of clinical samples has provided strong evidence that survivin expression predicts a reduced apoptotic index in tumors and poor patient survival (5,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Because of its differential expression in tumors versus normal tissues and its role in apoptosis for maintaining cell viability, survivin represents a promising drug target for cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Antisense Inhibition of Survivin Expression as a Cancer Therapeutic

Carrasco

Stamm

Marcusson

et al. 2011

Molecular Cancer Therapeutics

105

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Survivin, a family member of the inhibitor of apoptosis proteins that is expressed during mitosis in a cell cycle-dependent manner and localized to different components of the mitotic apparatus, plays an important role in both cell division and inhibition of apoptosis. Survivin is expressed in a vast majority of human cancers, but not in normal adult tissues. Survivin expression is often correlated with poor prognosis in a wide variety of cancer patients. These features make survivin an attractive target against which cancer therapeutics could be developed. We have identified a survivin antisense oligonucleotide (ASO) that potently downregulated survivin expression in human cancer cells derived from lung, colon, pancreas, liver, breast, prostate, ovary, cervix, skin, and brain as measured by quantitative RT-PCR and immunoblotting analysis. Specific inhibition of survivin expression in multiple cancer cell lines by this ASO (LY2181308) induced caspase-3-dependent apoptosis, cell cycle arrest in the G 2 -M phase, and multinucleated cells. We also showed that inhibition of survivin expression by LY2181308 sensitized tumor cells to chemotherapeutic-induced apoptosis. Most importantly, in an in vivo human xenograft tumor model, LY2181308 produced significant antitumor activity as compared with saline or its sequence-specific control oligonucleotide and sensitized to gemcitabine, paclitaxel, and docetaxel. Furthermore, we showed that this antitumor activity was associated with significant inhibition of survivin expression in these xenograft tumors. On the basis of these, LY2181308 is being evaluated in a clinical setting (Phase II) in combination with docetaxel for the treatment of prostate cancer.

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“…Much evidence has identified survivin as a prognostic marker for a variety of human cancers (39,40), including HNSCC (26,29,39). Recent findings have shown that survivin mediates resistance to cancer therapy; overexpression of survivin is correlated with resistance to radiotherapy or chemotherapy (39,41,42).…”

Section: Resultsmentioning

confidence: 99%

Insulin-like Growth Factor-I Receptor Signaling Pathway Induces Resistance to the Apoptotic Activities of SCH66336 (Lonafarnib) through Akt/Mammalian Target of Rapamycin–Mediated Increases in Survivin Expression

Jin

Kim

et al. 2008

Clinical Cancer Research

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Although preclinical studies have suggested that farnesyltransferase inhibitors (FTI) have promising antitumor activity, clinical trials have shown that FTI activity in patients is actually limited. The mechanism that induces resistance to FTI treatment is still not fully understood. The FTI SCH66336 has been shown to induce apoptotic and antiangiogenic activities in a subset of head and neck squamous cell carcinoma (HNSCC) and non^small cell lung cancer (NSCLC) cell lines. We therefore investigated the mechanisms mediating resistance to the therapeutic activities of SCH66336 in HNSCC and NSCLC. Our various analyses showed that insulin-like growth factor-I receptor (IGF-IR) activation interferes with the antitumor activity of SCH66336 in HNSCC and NSCLC cells. Treatment with SCH66336 activated the IGF-IR/phosphatidylinositol 3-kinase/Akt pathway, leading to increased mammalian target of rapamycin (mTOR)-mediated protein synthesis of survivin in a subset of HNSCC and NSCLC cell lines that were insensitive to the apoptotic activities of the drug. Inhibition of IGF-IR, Akt, or mTOR or the knockdown of survivin expression abolished resistance to SCH66336 and induced apoptosis in the cells. Overexpression of survivin by the use of adenoviral vector protected SCH66336-sensitive HNSCC cells from the apoptotic activities of the drug. Our results suggest that expression of phosphorylated IGF-IR, phosphorylated Akt, phosphorylated mTOR, and survivin serves as biological markers of SCH66336 responsiveness in HNSCC and NSCLC cells and that SCH66336 induces survivin expression through an IGF-IR/Akt/mTOR^dependent pathway. Thus, combining inhibitors of IGF-IR, phosphatidylinositol 3-kinase/Akt, mTOR, or survivin with SCH66336 may be an effective anticancer therapeutic strategy for patients with HNSCC or NSCLC.

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Survivin gene expression and prognosis in recurrent colorectal cancer Reply

Cited by 19 publications

References 4 publications

Tumor-specific gene expression using the survivin promoter is further increased by hypoxia

Tumor-specific gene expression using the survivin promoter is further increased by hypoxia

Antisense Inhibition of Survivin Expression as a Cancer Therapeutic

Insulin-like Growth Factor-I Receptor Signaling Pathway Induces Resistance to the Apoptotic Activities of SCH66336 (Lonafarnib) through Akt/Mammalian Target of Rapamycin–Mediated Increases in Survivin Expression

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