29LB1 Late Breaking ORAL Final safety, pharmacokinetic and antitumor activity results of a phase I study of YM155, a novel survivin inhibitor, when administered by 168 hour continuous infusion

Mita, Alain C.; Antonia, S.; Lewis, Lionel D.; Mahany, J. J.; Reddy, Nandi J.; Ricart, A.; Till, E.; Buell, Donald N.; Keating, Anne; Tolcher, A. W.

doi:10.1016/s1359-6349(06)70035-0

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“…The maximum tolerated dose was 4.8 mg/m 2 /d, the most frequent adverse events being pyrexia, arthralgias, nausea, fatigue, and diarrhea. Activity has been reported with three partial responses in non -Hodgkin's lymphoma, two prostate-specific antigen responses in hormone-refractory prostate cancer patients, and one minor response in non -small cell lung cancer (78). A second phase I study done in Japan with a similar dosing schedule but with i.v.…”

Section: Clinical-translational Advancesmentioning

confidence: 99%

Survivin: Key Regulator of Mitosis and Apoptosis and Novel Target for Cancer Therapeutics

Mita¹,

Mita²,

Nawrocki³

et al. 2008

Clinical Cancer Research

691

612

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Survivin, a member of the family of inhibitor of apoptosis proteins, functions as a key regulator of mitosis and programmed cell death. Initially, survivin was described as an inhibitor of caspase-9. However, over the last years, research studies have shown that the role of survivin in cancer pathogenesis is not limited to apoptosis inhibition but also involves the regulation of the mitotic spindle checkpoint and the promotion of angiogenesis and chemoresistance. Survivin gene expression is transcriptionally repressed by wild-type p53 and can be deregulated in cancer by several mechanisms, including gene amplification, hypomethylation, increased promoter activity, and loss of p53 function. This article reviews the multiple functions of survivin in the regulation of apoptosis, the promotion of tumorigenesis, and the development of survivin inhibitors as a novel anticancer therapeutic strategy.

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Section: Clinical-translational Advancesmentioning

confidence: 99%