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Vol 2|  Issue 2 | Apr – Jun 2023                                                                                      Indian J Pharm Drug Studies | 63 

Review Article 

The Potential of siRNA-Mediated Oncogene Silencing in Cancer Therapy: An 

Overview of Pharmacogenomics Strategies 

Preeti Shanbhag1, Ramdas Bhat2, A R Shabaraya3 

From 1PG Scholar, 2Assistant Professor, Department of Pharmacology, 3Principle and Head of the Department of Pharmaceutics, 

Srinivas College of Pharmacy, Valachil, Post Farangipete, Mangalore, Karnataka, India-574143. 

Correspondence to: Ramdas Bhat, Assistant Professor, Department of Pharmacology, Srinivas College of Pharmacy, Valachil, Post 

Farangipete, Mangalore, Karnataka, India. Email: ramdas21@gmail.com Tel.: +91 7795772463 

ABSTRACT  
 

siRNA-mediated silencing of oncogenes holds great promise as a potential cancer therapy. By selectively silencing genes involved in 

cancer progression, siRNA-based therapies have the potential to be highly specific and effective, while minimizing off-target effects 

and toxicity. However, several challenges need to be addressed before siRNA-based therapies can be widely used in clinical settings. 

One of the major challenges is the development of efficient and safe delivery systems for siRNAs. Additionally, more clinical trials are 

needed to evaluate the safety and efficacy of siRNA-based therapies for cancer treatment. Despite these challenges, ongoing research 

and development in the field of siRNA-based therapies are promising. New delivery systems, personalized medicine approaches, and 

combination therapies are being explored, which could potentially lead to more effective and personalized cancer treatment. With 

continued research and development, it is hoped that siRNA-based therapies will eventually become cancer treatments, providing 

patients with a more targeted and effective treatment option. 

Keywords: siRNA, Oncogenes, Cancer Therapy, Gene Silencing, Targeted Therapy, Delivery Systems. 

potent biological mechanism called RNA interference 

(RNAi) enables the post-transcriptional selective 

suppression of gene expression. This mechanism has 

undergone substantial research and has emerged as a potentially 

useful therapeutic tool for the management of a number of 

illnesses, including cancer [1]. Small interfering RNAs 

(siRNAs) are double-stranded RNA molecules that target and 

degrade particular mRNA regions to silence genes.  Oncogenes, 

which are genes that promote the growth and proliferation of 

cancer cells, have been discovered as promising targets for 

siRNA-mediated gene silencing in cancer therapy [2]. An 

enormous amount of work has gone into creating siRNA-based 

cancer medicines in recent years. The capacity of siRNAs to 

specifically target oncogenes offers a promising strategy for the 

creation of highly effective cancer treatments with little off-

target side effects. Moreover, siRNAs have the potential to 

address the drawbacks of conventional cancer therapies, such 

as chemotherapy medicines, which frequently exhibit low 

selectivity and high levels of toxicity [3]. An overview of the 

present status of siRNA-mediated oncogene silencing for 

cancer therapy will be given in this thorough review. The 

review will go over the various siRNA delivery methods, the 

difficulties faced by siRNA-based therapies, and the 

development of siRNA-based cancer therapy in the clinic [4]. 

Future developments in this area as well as the possibilities of 

siRNA-based cancer therapeutics will be covered. Ultimately, 

the goal of this study is to provide a thorough grasp of the status 

and potential applications of siRNA-mediated oncogene 

silencing for cancer therapy [5].

Fig No.1: Delivery systems for siRNA drug development in cancer therapy [6]

A 

mailto:ramdas21@gmail.com


Shanbhag et al.                                                            Cancer Therapy: An Overview of Pharmacogenomics Strategies 

Vol 2|  Issue 2 | Apr – Jun 2023                                                                                      Indian J Pharm Drug Studies | 64 

Different Approaches Used For Sirna Delivery For Cancer 

Therapy  

The development of siRNA-based cancer therapeutics faces 

significant challenges in the efficient delivery of siRNA to 

cancer cells. Delivering siRNAs to target cells can be difficult 

since they are generally big, negatively charged molecules that 

are prone to nuclease destruction [5]. Biological obstacles like 

the extracellular matrix, cellular membranes, and endosomal 

compartments must also be surmounted by the siRNA delivery 

mechanism. To get over these obstacles and make siRNA 

distribution to cancer cells easier, a number of strategies have 

been devised [7]. Lipid-based delivery systems one of the most 

widely used methods for siRNA distribution is lipid-based 

delivery systems. A hydrophobic core that can enclose siRNAs 

is often surrounded by a lipid bilayer in lipid nanoparticles [8]. 

These nanoparticles can passively gather in tumor tissues due 

to the improved permeability and retention impact because their 

size ranges from 20 to 100 nm (EPR). By integrating targeting 

moieties like antibodies, peptides, or aptamers, lipid-based 

delivery systems can also be designed to target particular cell 

types [9]. Polymer-based delivery systems are biodegradable 

polymers used to encase siRNAs in polymer-based delivery 

systems. These systems can be made to have different 

characteristics, such as size, charge, and hydrophobicity, which 

can influence how they are taken up by cells and transported 

within them. By adding targeting moieties, polymer-based 

systems can also be created to target particular cell types [10].  

Delivery methods based on inorganic nanoparticles for the 

transport of siRNA, and inorganic nanoparticles like gold, 

silica, and iron oxide have been researched. To make these 

particles easier for cancer cells to absorb, they can be 

functionalized with siRNAs and/or target molecules [11]. The 

special physicochemical characteristics of inorganic 

nanoparticles can be used to promote cellular absorption, 

endosomal escape, and gene silencing [12]. Viral vectors have 

been used to distribute siRNA because they are particularly 

effective in delivering genes to cells. However, because of 

safety issues such as immunogenicity and mutagenicity, their 

use is restricted. Usually, viral vectors are altered to lose their 

pathogenicity and designed to express siRNAs for certain 

targets [13]. Cell-penetrating peptides (CPPs) are short peptides 

that can penetrate cell membranes and facilitate the delivery of 

siRNAs into cells. CPPs can be fused to siRNAs to enhance 

their cellular uptake and endosomal escape. However, the 

delivery efficiency of CPPs is often low and is dependent on 

the type of CPP used [14]. Overall, each delivery system has its 

advantages and limitations, and the choice of delivery system 

will depend on the specific application and target. To overcome 

the challenges associated with siRNA delivery, researchers are 

continuing to develop new and innovative delivery strategies 

for siRNA-based cancer therapies. 

Fig No.2: Different approaches used for siRNA delivery for cancer therapy [15] 

Challenges Associated With siRNA-Based Therapies  

While siRNA-based therapies have shown great promise in 

preclinical studies and have advanced to clinical trials, there are 

still several challenges that need to be overcome to ensure their 

clinical success. As was already indicated, one of the main 

difficulties with siRNA-based therapeutics is getting siRNAs 

into the target cells. It is difficult to deliver siRNAs because 

they are big, negatively charged molecules that are vulnerable 

to nuclease destruction. A delivery mechanism that can shield 

siRNAs from deterioration, promote their cellular uptake, and 

guarantee their intracellular trafficking is necessary for 

effective siRNA delivery [16].  Although siRNAs are made to 

target particular genes, they can potentially have unwanted side 

effects. When siRNAs bind to undesired mRNA targets that 



Shanbhag et al.                                                            Cancer Therapy: An Overview of Pharmacogenomics Strategies 

Vol 2|  Issue 2 | Apr – Jun 2023                                                                                      Indian J Pharm Drug Studies | 65 

have partial sequence complementarity to the siRNA, off-target 

effects may result. Unwanted side effects may happen if 

undesired genes are silenced as a result of this [17]. siRNAs 

have the ability to elicit an immune response, which can result 

in the release of cytokines and chemokines that can cause 

cytotoxicity and inflammation. Although the immune system 

might become adapted to the siRNA delivery mechanism, this 

immune response can be particularly problematic for repeated 

siRNA treatment [18]. 

Because of their vulnerability to nuclease-mediated 

degradation, siRNAs have a short half-life in the bloodstream. 

Moreover, siRNAs' bioavailability can be decreased by the 

kidneys' quick clearance of the molecules. To enable the 

optimal distribution of siRNAs to target cells, the 

pharmacokinetics of these molecules must be adjusted [19]. 

Tumors are diverse, and various tumor cells may exhibit unique 

patterns of gene expression. Because of this, achieving uniform 

and efficient gene silencing across all tumor cells may be 

challenging. Because of the intricacy of siRNA production and 

delivery systems, siRNA-based medicines can be expensive to 

produce. The cost of production may restrict the accessibility 

of siRNA-based medicines and the scope of their extensive 

clinical use [20]. Overall, while siRNA-based therapies have 

great potential, there are still several challenges that need to be 

overcome to ensure their clinical success. Researchers are 

continuing to develop and refine siRNA delivery systems and 

optimize the pharmacokinetics of siRNAs to address these 

challenges and advance siRNA-based therapies to clinical 

practice. 

Clinical Progress of siRNA-Based Cancer Therapeutics  

siRNA-based cancer therapeutics have shown great promise in 

preclinical studies, but their translation to clinical practice has 

been challenging. Despite these challenges, several siRNA-

based cancer therapeutics have advanced to clinical trials [21]. 

Several siRNA-based therapies are currently being tested in 

humans for a range of cancer types, including ovarian, 

pancreatic, and liver cancer [21].   Patisiran can be used for the 

treatment of hereditary transthyretin-mediated amyloidosis 

(hATTR), a rare genetic condition that affects the heart and 

nervous system, patisiran is a siRNA-based therapy. In clinical 

trials, the drug patisiran—which inhibits the transthyretin 

gene—promisingly improved patient quality of life and nerve 

function [22]. A siRNA-based therapy called inclisiran is used 

to treat hypercholesterolemia. PCSK9, a protein that controls 

blood levels of LDL cholesterol, is the target of Inclisiran. 

Clinical trials on Inclisiran have yielded positive outcomes, 

with notable drops in LDL cholesterol levels [23].  

A siRNA-based therapy called ALN-TTRsc02 is being 

developed to treat ATTR amyloidosis. In clinical studies, the 

transthyretin gene-targeting drug ALN-TTRsc02 demonstrated 

encouraging outcomes with notable improvements in patient 

quality of life and nerve function [24].  QPI-1002 is used to 

avoid acute kidney injury, QPI-1002 is a siRNA-based therapy. 

In clinical studies, the p53 gene-targeting drug QPI-1002 had 

encouraging outcomes, significantly lowering the risk of acute 

renal damage in patients having heart surgery [25]. Although 

siRNA-based cancer treatments are currently in the early 

phases of clinical research, they have the potential to 

completely change the way cancer is treated. It is hoped that 

siRNA-based cancer treatments would advance and eventually 

become a standard component of cancer treatment with 

continued research and clinical studies [5].  

siRNA-Based Therapies For Cancer Treatment. The 

potential of siRNA-based therapies for cancer treatment is 

significant, and these therapies hold great promise for  

improving the effectiveness of cancer treatment. Targeted gene 

silencing is a very specific and exact siRNA-based therapeutics 

can be created to target particular genes that contribute to the 

development of cancer. This method of targeted gene silencing 

may help to lessen the toxicity and side effects of conventional 

cancer therapies like chemotherapy [26]. Potentially synergistic 

with other therapies where siRNA-based cancer therapies may 

be used in conjunction with other cancer therapies, such as 

chemotherapy or immunotherapy, to increase the efficacy of 

both. For example, siRNA-based therapeutics could be used to 

target genes that give resistance to chemotherapy, thus 

enhancing the efficacy of the chemotherapy [27].  

siRNA-based therapies can be designed to target a wide 

range of genes that play a role in cancer progression, including 

oncogenes, tumor genes, and genes involved in angiogenesis 

and metastasis. siRNA-based therapies can be customized for 

individual patients based on their genetic profile , which could 

potentially lead to more effective and personalized cancer 

treatment. siRNA-based therapies can be customized for 

individual patients based on their genetic  profile, which could 

potentially lead to more effective and personalized cancer 

treatment [28]. siRNA-based therapies can be customized for 

individual patients based on their genetic profile, which could 

potentially lead to more effective and personalized cancer 

treatment [27]. siRNA-based therapies are highly specific, 

which means that they have the potential to be less toxic than 

traditional cancer treatments, which can have significant side 

effects [5]. 

Despite these potential benefits, there are still several 

challenges associated with siRNA-based therapies, as 

discussed earlier. The delivery of siRNAs to target cells is one 

of the major challenges associated with siRNA-based therapies. 

Additionally, the high cost of manufacturing and the potential 

for off-target effects are also significant challenges that need to 

be addressed. Overall, siRNA-based therapies have the 

potential to significantly improve cancer treatment, but further 

research and development are needed to optimize their efficacy 

and safety. With ongoing research and clinical trials, it is hoped 

that siRNA-based therapies will continue to advance and 

eventually become a routine part of cancer treatment. 



Shanbhag et al.                                                            Cancer Therapy: An Overview of Pharmacogenomics Strategies 

Vol 2|  Issue 2 | Apr – Jun 2023                                                                                      Indian J Pharm Drug Studies | 66 

Fig No.3: Targeted gene silencing [29] 

Fig No.4: Synergistic chemotherapy towards breast cancer [30] 

Future Directions In the Field of Sirna-Mediated Silencing 

of Oncogenes for Cancer Therapy  

The field of siRNA-mediated oncogene silencing for cancer 

therapy is quickly developing, and it is moving in fascinating 

directions. Combining siRNA-based therapies with other 

cancer treatments, such as chemotherapy or immunotherapy, is 

one of the most promising areas of research. It might be 

possible to improve therapeutic outcomes by combining 

siRNA-based medicines with other cancer medications [31].  A 

key area of research focuses on delivering siRNAs to cancer 

cells in certain tissues. To deliver siRNAs to cancer cells in 

certain organs while limiting toxicity and off-target effects, 

researchers are creating innovative delivery mechanisms [32]. 

siRNA-based therapies can be customized for individual 

patients based on their genetic profiles. Developing methods to 

identify patient-specific targets and designing siRNAs that 

specifically target these genes is an area of active research [33].  

 Combating drug resistance is one of the main obstacles in 

the fight against cancer. To increase the efficiency of 

chemotherapy and other cancer treatments, researchers are 

investigating the potential of siRNA-based therapeutics to 

target genes that are involved in drug resistance [34]. The 

development of innovative delivery technologies that might 

increase the effectiveness of siRNA distribution is a key area of 

scientific interest. To improve the transport of siRNAs to target 

cells, researchers are experimenting with the use of 

nanoparticles, liposomes, and other technologies [35]. Further 

clinical trials are required to assess the security and 

effectiveness of siRNA-based treatments for the treatment of 

cancer. To maximize the clinical translation of siRNA-based 

therapeutics, ongoing research, and development are required 

[36]. Overall, the field of siRNA-mediated silencing of 

oncogenes for cancer therapy is rapidly advancing, and there is 

great potential for these therapies to significantly improve 

cancer treatment. With continued research and development, it 

is hoped that siRNA-based therapies eventually become integral 

to cancer treatment. 

Advantages of siRNA-Based Therapies for Cancer 

Treatment  

Very targeted and precise siRNA-based therapeutics can be 

created to target particular genes that contribute to the 

development of cancer [2]. SiRNA-based therapies have the 

potential to be utilized in conjunction with other cancer 

treatments like chemotherapy or immunotherapy to increase the 

efficacy of both [37]. siRNA-based cancer therapies can be 

created to target a multitude of genes, including oncogenes, 



Shanbhag et al.                                                            Cancer Therapy: An Overview of Pharmacogenomics Strategies 

Vol 2|  Issue 2 | Apr – Jun 2023                                                                                      Indian J Pharm Drug Studies | 67 

tumor suppressors, and genes involved in angiogenesis and 

metastasis, that are implicated in the development of cancer 

[38]. siRNA-based therapies have the potential to advance 

personalized medicine since they can be tailored for specific 

patients based on their genetic profiles, which may result in 

more efficient and specialized cancer treatment [39]. siRNA-

based therapies are highly specific, which means that they have 

the potential to be less toxic than traditional cancer treatments, 

which can have significant side effects [40]. 

Limitations of Sirna-Based Therapies for Cancer 

Treatment Include 

siRNAs are substantial, negatively charged molecules that are 

difficult to get through cell membranes. The creation of 

effective and secure siRNA delivery methods is a difficult task 

[41]. Possibility for harmful off-target effects: siRNA-mediated 

gene silencing may have unintended consequences on genes 

that are not intended targets [42]. siRNA-based medicines still 

have a high production cost, and patients have less access to 

them [43]. siRNAs have a short bloodstream half-life; regular 

dosing may be required [44]. Only a small number of siRNA-

based cancer medicines have moved to clinical trials, and none 

have received approval for use in humans despite extensive 

preclinical research [4]. Overall, while siRNA-based therapies 

hold great potential for improving cancer treatment, several 

challenges still need to be addressed before they become widely 

used in clinical settings. Ongoing research and development are 

necessary to optimize the efficacy, safety, and delivery of 

siRNA-based therapies. 

CONCLUSION 

siRNA-mediated cancer therapy has great potential for highly 

specific and effective treatment. However, efficient and safe 

delivery systems need to be developed, and more clinical trials 

are required for the evaluation of safety and efficacy. 

Researchers are working on developing new delivery systems, 

personalized medicine approaches, and combination therapies 

to overcome these challenges. Continued development of 

siRNA-based therapies could revolutionize cancer treatment, 

providing patients with targeted and effective options. 

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Vol 2|  Issue 2 | Apr – Jun 2023                                                                                      Indian J Pharm Drug Studies | 68 

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How to cite this article: Preeti Shanbhag, Ramdas Bhat, A 

R Shabaraya. The Potential of Sirna-Mediated Oncogene 

Silencing in Cancer Therapy: An Overview of 

Pharmacogenomics Strategies. Indian J Pharm Drug 

Studies. 2023: 2(2) 63-68. 

Funding: None                   Conflict of Interest: None Stated 

 

 

 

 

 


