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Survivin-Targeting Antisense Oligonucleotides in Cancer Therapy.
Bal Hari Poudel1,2,3, Suxiang Chen1,2, Rakesh N Veedu1,2,3
1Personalised Medicine Centre, Health Futures Institute, Murdoch University, Murdoch, WA 6150, Australia.
Molecules (Basel, Switzerland)
|July 15, 2026
Summary
Survivin (BIRC5) is a promising cancer target, but antisense oligonucleotides (ASOs) face challenges. Optimizing delivery and chemistry is crucial for effective cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Therapeutics
Background:
- Survivin (BIRC5) is overexpressed in cancers, promoting tumor survival and therapy resistance.
- Its absence in normal tissues makes survivin a selective cancer treatment target.
- Antisense oligonucleotides (ASOs) offer a precise method to silence survivin by targeting its mRNA.
Purpose of the Study:
- To review the role of survivin in cancer biology.
- To discuss the principles and development of survivin-targeting ASOs.
- To identify challenges and future directions for ASO therapeutics in cancer.
Main Methods:
- Review of preclinical and clinical studies on survivin-targeting ASOs.
- Analysis of ASO design, mechanisms of action, chemical modifications, and delivery strategies.
- Discussion of factors limiting clinical efficacy and safety.
Main Results:
- Preclinical studies show ASO-mediated survivin reduction inhibits tumor growth and enhances treatment sensitivity.
- Early clinical trials demonstrated target engagement but lacked consistent clinical benefit.
- Dose-limiting toxicities and inefficient delivery were identified as key limitations.
Conclusions:
- Survivin-targeting ASOs hold promise but require improved delivery systems and molecular chemistry for enhanced efficacy and safety.
- Addressing off-target effects and systemic toxicities is essential for clinical success.
- Optimized ASOs could enable personalized and combination cancer treatment strategies.
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