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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
Antisense treatment in human prostate cancer and melanoma
1Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
Abstract:
Antisense reagents and technology have developed as extraordinarily useful tools for analysis of gene function. The capacity of antisense to reduce expression of RNA (including protein-encoding mRNA and non-coding RNA) important in a multitude of diseases (including cancer) has led to the concept of using antisense molecules as drugs to treat those diseases. Both antisense RNA (RNAi) and antisense oligonucleotides (ASOs) are being developed for this purpose, with ASOs currently the most advanced in clinical testing. ASOs inhibit translation or induce degradation of complementary target RNA, and both Phase I and Phase II trials are either completed or in progress for a number of diseases. In this review, we focus on antisense approaches to treatment of two cancers (melanoma and hormone-resistant prostate cancer) where the early application of ASOs has provided important information revealing both potential for success and lessons for future preclinical and clinical investigation of ASOs as anti-cancer drugs. The progress of clinical application of two ASOs showing promise in treatment of human cancers--Oblimersen (G3139), targeting BCL2 for the treatment of metastatic melanoma, and Custirsen (OGX-11), targeting clusterin for the treatment of hormone refractory prostate cancer (HRPC)--is examined.
Insights
Antisense oligonucleotides (ASOs) show promise for treating cancers like melanoma and prostate cancer by reducing specific RNA expression. Clinical trials are evaluating ASOs, offering insights for future anti-cancer drug development.
Area of Science:
- Molecular Biology
- Oncology
- Pharmacology
Background:
- Antisense technology offers tools for gene function analysis.
- Antisense molecules can reduce disease-related RNA expression, including in cancer.
- Antisense RNA interference (RNAi) and antisense oligonucleotides (ASOs) are being developed as therapeutic agents.
Purpose of the Study:
- To review antisense approaches for treating melanoma and hormone-resistant prostate cancer.
- To examine the clinical progress of specific ASOs targeting BCL2 and clusterin.
- To highlight lessons learned from early ASO applications in cancer treatment.
Main Methods:
- Focus on antisense oligonucleotide (ASO) technology.
- Review of clinical trial data for ASOs in cancer therapy.
- Examination of ASOs targeting BCL2 (Oblimersen) and clusterin (Custirsen).
Main Results:
- ASOs inhibit translation or induce degradation of target RNA.
- Phase I and II trials for various diseases are ongoing or completed.
- Early ASO applications in melanoma and prostate cancer provide valuable insights.
Conclusions:
- ASOs represent a promising therapeutic strategy for cancer treatment.
- Oblimersen and Custirsen show potential in treating metastatic melanoma and hormone-refractory prostate cancer, respectively.
- Further preclinical and clinical investigations are crucial for optimizing ASO anti-cancer drug development.
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