Using Modified Guide Strands to Broaden Therapeutic Use of miRNAs for Breast Cancer

Ishmam Khan ’25

Figure 1: Triple-negative breast cancers are a significantly aggressive type of breast cancer, and are oftentimes resistant to existing chemotherapies. 

Triple-negative breast cancers (TNBCs) are a type of breast cancer that does not respond to traditional hormonal therapy. Despite TNBCs encompassing 10-20% of all breast cancers, TNBCs are significantly more aggressive than other breast cancers and have worse overall survival rates.  These cancers often offer patients a poor prognosis due to their high rates of proliferation and chemoresistance. A research group at the Renaissance School of Medicine at Stony Brook University has been working to find clinically effective treatments for TNBCs. In the past, they discovered a TNBC tumor suppressor guide strand gene called micron RNA-49 (miRNA-489) that was able to block the growth of TNBCs and mitigate DNA damaging responses (DDRs).  In their current study, these researchers aimed to broaden the therapeutic potential of miRNAs by using a modified guide strand, CMM489.

The researchers began by chemically modifying the existing guide strand of miRNA-489 by replacing the uracil base pair with 5-fluorouracil to combine the mitigation of TNBCS and DDRs into a single agent to test the inhibition of TNBC cell proliferation and tumor progression. They would then test this on a group of rats. The effects of this modified miRNA-489 would then be compared to that of the original. The CMM489 variant showed superior effects over miRNA-489 in inhibition of TNBC cell proliferation and tumor progression, inhibiting primary tumor growth in metastatic rat cells. Data showed that the CMM489 variant of mRNA displayed higher rates of resistance when subject to tumor growth in the group of rats. Hormone levels not only showed great potential in reducing potential cancer growth, but the mice also did not show any hair loss. This suggests that CMM489 is safe enough to be used as a potential therapy in addition to its efficacy. 

This research has laid the groundwork for clinical settings in using CMM489 as a therapeutic model for future TNBC samples. Chemotherapy with DNA damaging agents, for example, remains the primary treatment modality for treatment of primary and metastatic TNBCs. DDR inhibitors like the newly-proven CMM489 can greatly improve the effectiveness of chemotherapy and mitigate its side effects for the treatment of TNBCs. Indeed, along with further advancements in chemotherapy, clinical settings have much to benefit from implementing these new techniques.

Works Cited:

[1] YH. Soung, et al., Therapeutic potential of chemically modified miR-489 in triple-negative breast cancers. Cancers. 12, 8 (2020) doi: 10.3390/cancers12082209

[2] Image retrieved from: https://commons.wikimedia.org/wiki/File:Breast_Cancer_Awareness_(263497131).jpg 

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