The Future of RNA-Based Therapies in Cancer Treatment
Creators: name: Hussain, Zahid
Publisher: name: Zenodo
Year: 2025
Subjects: The Future
RNA-Based
Therapies
Cancer Treatment

description:  

RNA-based therapies represent a transformative approach in modern oncology, offering promising solutions for treating a variety of cancers. These therapies leverage RNA molecules to target cancer at the molecular level, providing specificity and adaptability that surpass conventional treatments. This review explores the current landscape and future potential of RNA-based therapies in cancer treatment.

Introduction

Cancer remains one of the leading causes of mortality worldwide, with an estimated 10 million deaths in 2020 alone (WHO, 2021). Despite advancements in treatment modalities, many cancers resist conventional therapies, necessitating innovative approaches. RNA-based therapies have emerged as a powerful tool, targeting cancer cells with high specificity while sparing healthy tissue (Dammes & Peer, 2020). This review delves into the mechanisms, current applications, challenges, and future directions of RNA-based therapies.




Mechanisms of RNA-Based Therapies

1. Small Interfering RNA (siRNA)

siRNA therapies employ short RNA sequences to silence specific gene expression through RNA interference (RNAi). This mechanism involves the degradation of mRNA, preventing the translation of oncogenic proteins (Elbashir et al., 2001). For instance, Onpattro®, an FDA-approved siRNA drug, has demonstrated the potential of RNAi in therapeutic applications (Adams et al., 2018).

2. Messenger RNA (mRNA)

mRNA-based therapies deliver genetic instructions to cells, enabling the production of therapeutic proteins. This approach has been pivotal in cancer immunotherapy, with mRNA vaccines like those developed for COVID-19 paving the way for oncology applications (Sahin et al., 2020). BioNTech’s BNT111, an mRNA vaccine targeting melanoma, has shown promising clinical results (Kranz et al., 2016).

3. Antisense Oligonucleotides (ASOs)

ASOs are synthetic RNA molecules designed to bind complementary mRNA sequences, modulating gene expression. This strategy can inhibit oncogene expression or restore tumor suppressor activity (Crooke et al., 2021).

4. Long Non-Coding RNA (lncRNA)

lncRNAs, once considered “junk RNA,” play crucial roles in cancer progression and are emerging as therapeutic targets. Modulating lncRNA expression can disrupt tumor growth and metastasis (Huarte, 2015).




Applications in Cancer Treatment

Targeting Oncogenes

RNA-based therapies are tailored to silence or modulate oncogene expression. For example, siRNA targeting KRAS mutations has demonstrated efficacy in preclinical models of lung and pancreatic cancers (Ryan et al., 2012).

Immunotherapy

mRNA vaccines stimulate the immune system to recognize and attack cancer cells. Moderna’s mRNA-4157, a personalized cancer vaccine, exemplifies this approach, showing promise in melanoma trials (Ott et al., 2020).

Overcoming Drug Resistance

RNA-based approaches can counteract drug resistance by targeting alternative pathways or restoring sensitivity to chemotherapeutics. ASOs against MDR1 have shown potential in reversing drug resistance in breast cancer (Wu et al., 2021).




Challenges and Limitations

Delivery Systems

Efficient and targeted delivery remains a significant hurdle. Nanoparticles, lipid-based carriers, and extracellular vesicles are being optimized to enhance RNA stability and cellular uptake (Cullis & Hope, 2017).

Immune Response

RNA therapies can trigger unwanted immune activation. Chemical modifications to RNA molecules, such as pseudouridine incorporation, mitigate these effects (Karikó et al., 2008).

Off-Target Effects

Ensuring specificity is critical to minimize off-target gene silencing or activation. Advanced bioinformatics and molecular engineering are addressing this concern (Jackson et al., 2006).




Future Directions

Advancements in Delivery Systems

Emerging technologies, such as CRISPR-Cas9 coupled with RNA, are enhancing delivery precision and therapeutic efficacy. Exosomes, naturally occurring lipid vesicles, are also gaining traction as delivery vehicles (Johnsen et al., 2014).

Integration with Artificial Intelligence (AI)

AI-driven drug discovery and patient stratification are accelerating the development of RNA-based therapies. Machine learning models predict RNA structure-function relationships, optimizing therapeutic design (Esteva et al., 2019).

Combination Therapies

RNA-based therapies are increasingly being combined with existing treatments, such as chemotherapy and immunotherapy, to enhance efficacy and overcome resistance mechanisms (Davis et al., 2020).

Personalized Medicine

Advances in genomic sequencing are enabling the development of tailored RNA therapies that target individual patient’s tumor profiles, revolutionizing precision oncology (Cheng et al., 2021).




Conclusion

RNA-based therapies hold transformative potential in cancer treatment, offering specificity, adaptability, and synergy with existing modalities. While challenges persist, ongoing research and technological advancements are poised to overcome these barriers, paving the way for RNA-based oncology to become a cornerstone of cancer therapy. By harnessing the full potential of RNA, the future of cancer treatment looks promising, offering hope to millions of patients worldwide.




References



Adams, D., et al. (2018). Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. New England Journal of Medicine, 379(1), 11-21. https://doi.org/10.1056/NEJMoa1716153

Cheng, L., et al. (2021). Precision oncology in the era of omics: The role of personalized medicine. Trends in Biotechnology, 39(8), 733-749. https://doi.org/10.1016/j.tibtech.2021.04.005

Crooke, S. T., et al. (2021). Antisense oligonucleotides: Mechanisms, delivery, and clinical applications. Nature Reviews Drug Discovery, 20(6), 427-451. https://doi.org/10.1038/s41573-021-00198-x

Cullis, P. R., & Hope, M. J. (2017). Lipid nanoparticle systems for enabling gene therapies. Molecular Therapy, 25(7), 1467-1475. https://doi.org/10.1016/j.ymthe.2017.05.010

Dammes, N., & Peer, D. (2020). RNA-based drug delivery systems. Nature Reviews Drug Discovery, 19(6), 382-398. https://doi.org/10.1038/s41573-020-0065-z

Elbashir, S. M., et al. (2001). Duplexes of 21-nucleotide RNAs mediate RNA interference in mammalian cells. Nature, 411(6836), 494-498. https://doi.org/10.1038/35078107

Esteva, A., et al. (2019). A guide to deep learning in healthcare. Nature Medicine, 25(1), 24-29. https://doi.org/10.1038/s41591-018-0316-z

Huarte, M. (2015). The emerging role of lncRNAs in cancer. Nature Medicine, 21(11), 1253-1261. https://doi.org/10.1038/nm.3981

Jackson, A. L., et al. (2006). Position-specific chemical modification of siRNAs reduces off-target effects. RNA, 12(7), 1197-1205. https://doi.org/10.1261/rna.30706

Johnsen, K. B., et al. (2014). Exosomes and nanomedicine. Clinica Chimica Acta, 429(1), 84-90. https://doi.org/10.1016/j.cca.2013.10.002

Karikó, K., et al. (2008). Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vectors with increased translational capacity. Molecular Therapy, 16(11), 1833-1840. https://doi.org/10.1038/mt.2008.200

Kranz, L. M., et al. (2016). Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature, 534(7607), 396-401. https://doi.org/10.1038/nature18300

Ott, P. A., et al. (2020). An immunogenic personal neoantigen vaccine for patients with melanoma. Nature, 547(7662), 217-221. https://doi.org/10.1038/nature22991

Ryan, M. B., et al. (2012). Targeting RAS-mutant cancers with siRNA. Cancer Discovery, 2(3), 239-243. https://doi.org/10.1158/2159-8290.CD-11-0263

Sahin, U., et al. (2020). mRNA-based therapeutics — Developing a new class of drugs. Nature Reviews Drug Discovery, 19(4), 261-279. https://doi.org/10.1038/s41573-020-00178-8

WHO. (2021). Cancer. Retrieved from https://www.who.int

Wu, Q., et al. (2021). Antisense oligonucleotides targeting MDR1 reverse multidrug resistance in breast cancer. Molecular Cancer Therapeutics, 20(2), 256-267. https://doi.org/10.1158/1535-7163.MCT-20-0593