Researchers at Baylor College of Medicine and other institutions have identified a potential new drug target for the treatment of triple-negative breast cancer (TNBC). TNBC is an aggressive form of breast cancer with limited therapeutic options and a poor prognosis. The team focused on a protein called eIF4A, which plays a crucial role in the production of proteins that promote cancer growth.
In their study, the researchers used a small molecule drug called Zotatifin to target eIF4A. They found that Zotatifin effectively suppressed tumor cell proliferation by inhibiting the production of tumor-promoting proteins. Additionally, the drug also remodelled the tumor immune microenvironment, making it more favorable for tumor elimination.
These promising findings suggest that targeting eIF4A with Zotatifin could lead to novel therapies for TNBC and improved patient outcomes. The researchers propose conducting clinical trials to further assess the potential benefits of this approach.
The study also investigated the combination of Zotatifin with chemotherapy and immunotherapy. The researchers observed increased DNA damage and cell death when Zotatifin was combined with the chemotherapy drug carboplatin. Furthermore, the combination treatment altered the composition of immune cells within the tumor, favoring the recruitment of tumor-fighting cells over tumor-protecting cells.
This change is significant because TNBC tumors typically have more immune cells that protect the tumor rather than fight it. This makes immunotherapies less effective. However, Zotatifin transformed these “cold tumors” into “hot tumors” by increasing the presence of cancer-fighting immune cells. This change sensitized the tumors to immune checkpoint blockade, a type of immunotherapy, and improved the overall treatment.
Combining Zotatifin with carboplatin also resulted in significantly better outcomes compared to each treatment alone, prolonging survival in animal models. Additionally, the researchers discovered that the small molecule drug allowed for the use of lower doses of chemotherapy, reducing toxicities and negative side effects.
The findings of this study provide hope for improving treatments for patients with TNBC. By targeting eIF4A with Zotatifin and combining it with chemotherapy and immunotherapy, it may be possible to enhance the efficacy of treatment and reduce the negative side effects associated with current therapies. Further research and clinical trials are needed to validate these findings and determine the potential benefits for TNBC patients.
1. Source: Coherent Market Insights, Public sources, Desk research
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