Zolinza Reduces Brain Metastases in Mice

ZolinzaIn a new study, Merck’s drug vorinostat (Zolinza), a histone deacetylase inhibitor also known as suberoylanilide hydroxamic acid (SAHA), was able to cross the blood-brain barrier and reduce the development of large metastatic tumors in mice brains by 62% when compared with mice not receiving the drug. Vorinostat is approved to treat patients with cutaneous T-cell lymphoma. The incidence of breast cancer drug spread to the brain is increasing. These metastases have been largely untreatable because the blood-brain barrier limits drug access to the brain and many drugs are carried out of the brain at this barrier. Vorino-stat appears to slow the growth of primary tumors of several different types of cancer treatment in mice. Previous studies suggested that the drug could be taken up by the brain, but little was known about its effects on metastatic tumors. To study the drug’s effect on the formation of brain metastases, scientists used a mouse model of human breast cancer. Human breast cells were cultured in the laboratory and were injected into mice with compromised immune systems. The breast cheap cancer cells then migrated to the brain, forming metastases.

Urgently needed are medications that can cross the blood-brain barrier and reduce the size and incidence of metastatic tumors. Vorino-stat was easily absorbed into normal mouse brains and reduced the development of tiny tumors by 28% compared with the rate in control mice. Vorinostat’s action may be linked to the fact that it can cause breaks in both strands of a DNA helix and can lower the activity of a DNA repair gene called Rad52. The researchers hypothesize that the inability of the cancer cells to repair DNA damage would then slow the rate of tumor cell metastasis. Earlier research showed that vorino-stat could enhance the effect of radiation therapy in mice with brain cancer metastasis. Mice that received implants of human breast tumors in their brains lived the longest after receiving both vorino-stat and radiation, suggesting that the drug enhances the sensitivity of cancer cells to radiation therapy. Sources: Clin Cancer Res2009;15(19); NIH, September 29, 2009