Gene silencing concept illustration

Beating Cancer's Resistance: Can Silencing Genes Make Treatment Work Better?

Author's portrait.
Kai Mendoza in Health & Wellness August 2025 • 4 min read.

"New research explores how targeting specific genes could make stubborn cancers more vulnerable to existing treatments, offering hope for improved outcomes."


For many facing colorectal cancer, the drug oxaliplatin offers a lifeline, improving response rates and extending survival. However, a significant challenge remains: a large number of patients either don't respond well initially or develop resistance over time. This has spurred researchers to seek new strategies to boost the effectiveness of this important treatment.

One promising avenue involves understanding and targeting the genes that enable cancer cells to resist oxaliplatin. Scientists are particularly interested in how manipulating these genes might make cancer cells more vulnerable to the drug, leading to better outcomes.

Recent research has focused on a technique called RNA interference (RNAi) to 'silence' specific genes that contribute to drug resistance. By carefully selecting which genes to target, scientists hope to disrupt the mechanisms that protect cancer cells, making them more susceptible to oxaliplatin's effects. This article will explore the findings of a study that investigated this approach, offering insights into potential new treatment strategies.

Silencing the Resistance: Targeting clAP2 and LIVIN

Gene silencing concept illustration

Researchers designed a study to identify key genes that become more active when cancer cells are exposed to oxaliplatin. They focused on genes involved in pathways that prevent cell death (apoptosis), reduce stress within the cell, and handle drug metabolism. The goal was to find the most responsive targets for gene silencing.

The study pinpointed two genes, cIAP2 and LIVIN, as showing the most significant increase in activity during oxaliplatin treatment. These genes produce proteins that inhibit caspase 3 and 9, key components of the cell's self-destruct mechanism. By blocking these proteins, cancer cells can avoid apoptosis and survive the effects of the drug.

  • cIAP2: A well-known target of the c-Myc protein, often elevated in lung, colon, and pancreatic cancers. It directly inhibits caspase 3 and 9, preventing apoptosis.
  • LIVIN: While less studied than cIAP2, LIVIN also inhibits caspases and plays a role in preventing cell death.
To test the impact of silencing these genes, the researchers used small interfering RNA (siRNA) to specifically target and reduce the activity of cIAP2 and LIVIN in HCT-116 colon cancer cells. The results were striking: silencing either cIAP2 or LIVIN independently doubled the cells' sensitivity to oxaliplatin. Even more impressively, silencing both genes together led to a five-fold increase in sensitivity.

A Promising Path Forward

This research demonstrates the potential of targeting specific genes with siRNA to overcome drug resistance in cancer. By silencing cIAP2 and LIVIN, researchers were able to significantly increase the sensitivity of colon cancer cells to oxaliplatin, a commonly used chemotherapy drug.

The study's dose-dependent approach to identifying reliable targets is particularly noteworthy. By carefully observing gene expression changes at different oxaliplatin concentrations, the researchers were able to pinpoint the most relevant targets for siRNA silencing.

While further research is needed, these findings suggest that combining traditional chemotherapy with gene silencing techniques could offer a more effective strategy for treating colorectal cancer and potentially other cancers that develop resistance to drug treatments. This approach opens new avenues for developing personalized cancer therapies that target the specific mechanisms driving drug resistance in individual patients.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

1

What is oxaliplatin, and why is there a need to improve its effectiveness?

Oxaliplatin is a chemotherapy drug used to treat colorectal cancer. It helps improve response rates and extends survival for many patients. However, some patients don't respond well initially, or they develop resistance over time, which prompts researchers to explore ways to make the treatment more effective.

2

Which specific genes were identified as key targets for silencing in the study, and what roles do they play in cancer cell survival?

The study focused on cIAP2 and LIVIN. cIAP2 is a target of the c-Myc protein and is often elevated in lung, colon, and pancreatic cancers. LIVIN, while less studied, also inhibits caspases and prevents cell death. Silencing these genes makes cancer cells more vulnerable to oxaliplatin.

3

How does RNA interference (RNAi) and specifically siRNA work to combat drug resistance in cancer cells, and which genes are targeted?

RNA interference (RNAi) is used to 'silence' specific genes that contribute to drug resistance. Small interfering RNA (siRNA) is used to target and reduce the activity of specific genes like cIAP2 and LIVIN. This disruption makes cancer cells more susceptible to the effects of oxaliplatin.

4

What was the impact on cancer cells' sensitivity to oxaliplatin when cIAP2 and LIVIN were silenced individually versus when they were silenced together?

When cIAP2 or LIVIN were silenced independently, the colon cancer cells' sensitivity to oxaliplatin doubled. When both genes were silenced together, the sensitivity to oxaliplatin increased five-fold. This indicates that targeting both genes simultaneously could be a particularly effective strategy for overcoming drug resistance.

5

How do cIAP2 and LIVIN prevent apoptosis in cancer cells, and why is this important in the context of chemotherapy resistance?

cIAP2 and LIVIN produce proteins that inhibit caspase 3 and 9. Caspase 3 and 9 are key components of the cell's self-destruct mechanism, called apoptosis. By inhibiting caspase 3 and 9, cancer cells can avoid apoptosis and survive the effects of chemotherapy drugs like oxaliplatin. Targeting cIAP2 and LIVIN allows the cell to self-destruct more readily.

Newsletter Subscribe

Subscribe to get the latest articles and insights directly in your inbox.