An RNA molecule contributes to therapy resistance of triple negative breast cancer
Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Chemotherapy before or after surgery remains the standard treatment regimen for stage I–III TNBC. Only a small portion of patients can benefit from targeted therapy with PARP inhibitors because of BRCA mutations. However, resistance to chemotherapy or targeted therapy remains a major hurdle.
Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that currently has limited treatment options. Standard therapy involves chemotherapy before or after surgery, but only a small fraction of patients respond to targeted PARP inhibitor therapy due to BRCA mutations. Despite this, chemotherapy and targeted therapy resistance remain significant challenges.
In a recent study published in the Journal of Biomedical Science, researchers from National Taiwan University, Academia Sinica, and Taipei Medical University discovered that a long noncoding RNA molecule, Smyca, contributes to therapy resistance in TNBC. Smyca is a long noncoding RNA (lncRNA) that is expressed at high levels in TNBC cells.
The researchers found that Smyca becomes even more abundant when TNBC cells are treated with DNA damage-inducing therapies. Smyca works in conjunction with the oncogenic transcription factor FOXM1 to promote DNA repair and nucleotide metabolism genes. This allows tumor cells to recover from treatment-induced DNA damage, rendering them resistant to chemotherapy and targeted therapy.
To demonstrate this mechanism, the researchers used antisense RNA and nanoparticle-assisted delivery to block Smyca function. This approach significantly inhibited DNA repair and made TNBC tumors more susceptible to chemotherapy and targeted therapy. Moreover, Smyca targeting activated the immune system, converting an immune-cold tumor microenvironment into an immune-hot one, which enhances the effectiveness of immunotherapy in treating stage IV TNBC.
This research highlights the potential of targeting the Smyca-FOXM1 ribonucleoprotein complex as a therapeutic strategy to overcome treatment resistance and enhance the immune response against TNBC.
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