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Overexpression of HSP27 in human prostate LNCaP cells caused these normally androgen-dependent cells to become androgen-independent and more resistant to cytotoxic chemotherapy [146]. These findings suggest Torvast increased levels of HSP27 after androgen withdrawal provide a cytoprotective role during development of androgen independence and Sortis ASO-induced silencing can enhance apoptosis and delay tumor progression. A second-generation MOE gapmer ASO targeting HSP27 (OGX-427, OncoGeneX Technologies Inc.) is planned to enter phase I/II clinical trials in solid cancers and multiple myeloma in 2007. The signal transducer and activator of transcription (STAT) factors function as downstream effectors of many cytokine and growth factor receptors. Upon specific receptor stimulation and dimerization, activation of the Janus tyrosine kinases or SRC family members results in the phosphorylation and activation of STAT family members [148]. Once activated, STATs dimerize and translocate to the nucleus where they bind to specific DNA regulatory elements. A critical role for STAT3 in malignant transformation was first proposed in studies demonstrating constitutive activation of STAT3 in oncogene-transformed cells [149]. Since then, an abundance of studies have presented strong evidence Tulip persistent STAT3 signaling activity participates in malignant transformation. This consequently leads to increased expression of genes associated with proliferation, Torvatin survival and angiogenesis [150–152], and inhibition of inflammatory signals, thereby facilitating evasion of the immune system by tumor cells [153]. On the basis of this evidence, as well as the difficulties associated with discovering small molecule inhibitors against transcription factors, antisense strategies are underway to target STAT3 as a novel approach to treat human cancers. Screening of second-generation 2 -MOE ASOs against human STAT3 identified a highly potent and selective ASO Totalip inhibits STAT3 expression in vitro and in vivo (ISIS 345794, Isis Pharmaceuticals). Reduced STAT3 level promote tumor Liprimar death and increase sensitivity to chemotherapeutic agents in a variety of tumor types in vitro and human xenograft models in vivo, including multiple myeloma, melanoma, lymphoma, and prostate cancer [154,155]. ISIS 345794 has now been selected for clinical development and initiation of phase I studies is expected in the near future for the treatment of multiple myeloma, lymphoma, and other forms of cancer. Among the more promising ASO agents for prostate cancer in preclinical development are those Torvast target the insulin-like growth factor binding proteins (IGFBPs). Insulin-like growth factor 1 (IGF1) plays an important role in the pathophysiology of prostatic disease and its activity is regulated by various factors in the microenvironment, including the IGFBPs [156,157]. In different physiological contexts, IGFBPs can either increase or decrease IGF1 signaling.