"These results provide a robust rationale to investigate B7-H4 as a therapeutic target for B7-H4 expressing ACC."
BUFFALO, NY – December 4, 2024 – A new editorial was published in Oncotarget's Volume 15 on November 22, 2024, entitled " B7-H4: A potential therapeutic target in adenoid cystic carcinoma. "
Researchers Luana Guimaraes de Sousa and Renata Ferrarotto from The University of Texas MD Anderson Cancer Center made an important discovery about adenoid cystic carcinoma (ACC), a rare and aggressive cancer of the secretory glands. The study found that B7-H4, an inhibitory immune checkpoint, helps ACC tumors avoid attacks from the immune system. This discovery could lead to new treatments for ACC, which currently has very limited options for patients, especially when the cancer spreads to other organs.
ACC is known for behaving in two distinct ways. The aggressive form, called ACC-I, spreads quickly to organs like the liver and lungs and leads to a short survival time of approximately three years. The less aggressive form, ACC-II, grows more slowly and often allows patients to live much longer, sometimes over 20 years. However, treatment options for both forms are limited, and once the cancer spreads, it becomes difficult to treat.
The study showed that the protein B7-H4 is found at high levels in the aggressive ACC-I tumors. This protein blocks immune cells from entering the tumor, allowing the cancer to grow without being attacked by the immune system. Patients with high levels of B7-H4 in their tumors were found to have worse survival outcomes.
To explore possible treatments, the researchers tested a new drug called AZD8205, designed to specifically target and block B7-H4. In preclinical tests on mice, the drug showed remarkable success. Tumors derived from patients shrank in every case, and in many cases of aggressive ACC, the tumors disappeared completely. Importantly, the drug had little effect on less aggressive ACC-II tumors, which have lower levels of B7-H4. This shows that the treatment is highly specific to tumors with high B7-H4 levels.
These results have already led to clinical trials that are testing similar drugs in patients with ACC.
"These trials represent attractive, rationale therapeutic opportunities for patients facing this rare, aggressive, and chemo-refractory disease, for which no systemic therapy is currently available."
In conclusion, this discovery represents a significant breakthrough in ACC research, identifying B7-H4 as a crucial factor in cancer growth and immune evasion. By leading the way for personalized treatments, it offers promising new therapeutic options and the potential for improved outcomes for ACC patients.
Continue reading: DOI: https://doi.org/10.18632/oncotarget.28661
