Gene expression silencing therapy in tumors, focus on gastrointestinal and genitourinary tumors

Area of Science:

• Molecular Biology
• Genetics
• Oncology

Background:

• Precision oncology utilizes oligonucleotide-based therapies for gene expression silencing.
• Antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and microRNAs (miRNAs) offer targeted genetic approaches.
• These therapies show potential for overcoming resistance in conventional cancer treatments and targeting 'undruggable' genetic elements.

Purpose of the Study:

• To review the structural features, mechanisms of action, and clinical applications of ASOs, siRNAs, and miRNAs.
• To focus on the application of these oligonucleotide therapies in gastrointestinal and genitourinary cancers.
• To highlight advancements and challenges in the clinical translation of oligonucleotide-based cancer treatments.

Main Methods:

• Review of existing literature on oligonucleotide therapy development and application.
• Analysis of chemical modifications and delivery systems enhancing oligonucleotide stability and cellular uptake.
• Examination of clinical trial data for siRNA-based therapies targeting oncogenes.

Main Results:

• Oligonucleotide therapies demonstrate high precision in targeting specific genetic sequences for gene silencing.
• Chemical modifications and advanced delivery systems (lipid nanoparticles, GalNAc conjugates) improve therapeutic stability and efficacy.
• siRNA-based therapies targeting oncogenes show promising results in clinical trials for cancer treatment.

Conclusions:

• Oligonucleotide-based therapies represent a significant advancement in precision oncology, offering novel treatment strategies.
• Despite challenges like degradation and cellular uptake, ongoing innovations are enhancing their clinical viability.
• Continued research and development in oligonucleotide therapies promise more effective and safer cancer treatments, particularly for gastrointestinal and genitourinary malignancies.