Inducing Tumor Cell Death by RIG-I: The Future of Breast Cancer?

By Riya Gandhi ‘22

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Figure 1. Breast cancer is one of the most common cancers affecting women worldwide.

In recent years cancer therapy – especially cancer immunotherapy – has gained momentum and scientists’ interest has turned to immune checkpoint inhibitors (ICIs). ICIs aid in the suppression of checkpoint receptors to produce powerful immune responses against tumors. Although such a procedure is gaining momentum in clinical settings, much research must be done to legitimize this treatment for breast cancer. Under principle investigator David L. Elion of Vanderbilt University’s School of Medicine, researchers were able to induce a formidable gene that monitors and kills breast cancer tumors.

The primary goal of these researchers was to determine the efficiency of a pattern-recognition receptor known as retinoic acid-inducible gene I (RIG-I). First, they synthesized a RIG-I ligand from a minimal 50-triphophosphorylated stem-loop RNA (SLR) sequence. This ligand activates the RIG-I agonist and translocates it to the mitochondria, where it interacts with mitochondrial antiviral signaling proteins to activate pathways that produce inflammatory cytokines. Next, the researchers utilized breast cancer cells and Western analysis to examine RIG-I and genomic deletion and found that expression of RIG-I does not typically fail. The researchers discovered that activation of RIG-I in vivo decreased breast tumor growth and metastasis. More importantly, RIG-I signaling induces apoptosis and pyroptosis, which are two forms of programmed cell death in breast cancer cells.

Not only did this experiment provide a promising method for breast cancer treatment, but it also uncovered a deeper understanding of the functions of certain genes. In the future, these findings may become the foundation of leading treatment for other forms of cancer; however, there is still much research to be done regarding its potential.

 

References

  1. D. Elion, et. al., Therapeutically active RIG-I agonist induces immunogenic tumor cell killing in breast cancers. Cancer Research 78, 6183-6195 (2018). doi: https://doi.org/10.1158/0008-5472.can-18-0730.  
  2. Image retrieved from: https://www.pexels.com/photo/579474/
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