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SPC3042: a proapoptotic survivin inhibitor
Jens Bo Hansen1, Niels Fisker, Majken Westergaard
1Research Division, Santaris Pharma A/S, Boege alle 3, Hoersholm 2970 Denmark. bh@santaris.com
Molecular Cancer Therapeutics
|September 16, 2008
Summary
A new locked nucleic acid (LNA) oligonucleotide, SPC3042, effectively inhibits survivin, a key cancer target. This leads to cancer cell death and enhances chemotherapy effectiveness in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cellular homeostasis, regulated by apoptosis and cell division, is vital for life.
- Dysregulation of these processes is linked to cancer.
- Targeting cancer-specific molecular dependencies is key for effective cancer therapy.
Purpose of the Study:
- To introduce and characterize SPC3042, a novel antisense inhibitor of survivin.
- To compare SPC3042's properties with the existing antisense drug LY2181308/ISIS23722.
- To evaluate SPC3042's therapeutic potential in cancer treatment.
Main Methods:
- Design and synthesis of SPC3042, a 16-mer locked nucleic acid (LNA) oligonucleotide.
- Assessment of survivin mRNA inhibition and its downstream effects (cell cycle arrest, apoptosis, Bcl-2 levels).
- In vitro and in vivo evaluation of SPC3042's efficacy and its sensitizing effect on Taxol treatment in prostate cancer models.
Main Results:
- SPC3042 demonstrates enhanced nuclease stability and potency for survivin mRNA inhibition due to LNA modifications.
- Down-regulation of survivin by SPC3042 induces cell cycle arrest and apoptosis, and reduces Bcl-2 expression.
- SPC3042 sensitizes prostate cancer cells to Taxol, improving treatment efficacy both in vitro and in vivo.
Conclusions:
- SPC3042 is a potent antisense inhibitor of survivin with improved properties over previous generations.
- SPC3042 effectively induces cancer cell death and enhances the efficacy of standard chemotherapy.
- SPC3042 represents a promising therapeutic candidate for cancer treatment, particularly prostate cancer.
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