Triple-negative breast cancer (TNBC) is a particularly aggressive and difficult-to-treat form of breast cancer that lacks estrogen, progesterone, and HER2 receptors. This lack of targetable receptors limits treatment options, leading to worse prognoses for TNBC patients. However, a recent study conducted by Zachary Schug, Ph.D., and his team at The Wistar Institute has shown a promising double-acting mechanism for combating TNBC.
The study focused on silencing a gene called ACSS2, which regulates the nutrient acetate that TNBC cells rely on to grow and spread. Using CRISPR-Cas9 gene editing and a powerful ACSS2 inhibitor called VY-3-135, the researchers were able to deactivate ACSS2 and impair TNBC metabolism. This not only hindered the cancer’s ability to grow, but it also triggered the immune system to recognize and attack the cancer.
One interesting aspect of this approach is that cancer cells with inhibited ACSS2 cannot process acetate effectively, leading to an accumulation of acetate in the tumor region. This accumulation acts as a signal to the immune system, alerting it to the presence of the cancer.
The process of guiding the immune system to the cancer, known as “immunosensitization,” has been a challenge in TNBC research. However, Schug’s study demonstrated that ACSS2 inhibition effectively immunosensitizes against TNBC, resulting in a significant reduction in tumor growth. In some cases, the cancer was completely eradicated.
Schug believes that this double-acting treatment approach could greatly improve outcomes for TNBC patients with limited treatment options. The combination of ACSS2 inhibitors with standard chemotherapy has shown enhanced effectiveness, opening up new possibilities for future treatments.
While more research is needed, this study highlights the potential of targeting ACSS2 as a promising strategy to combat TNBC. Other researchers are also exploring ACSS2 inhibitors, and clinical trials are underway. With continued studies and the combination of different treatment approaches, significant advancements in treating TNBC are expected.
Zachary Schug et al. “Acetate acts as a metabolic immunomodulator by bolstering T-cell effector function and potentiating antitumor immunity in breast cancer.” Nature Cancer. (2023).