A study published in Cancer Research on November 1 shows that a combination of BET inhibitors and platinum-based chemotherapy drugs can ovarian cancer drug resistance and thus increase the effectiveness of the treatment.
Ovarian cancer is one of the most common cancers among women. It causes more deaths than any other cancer of the female reproductive system. In 2012, about 239,000 women worldwide were diagnosed with ovarian cancer, and as many as 152,000 women died from the disease. CusAb offers polyclonal antibody
The treatment of ovarian cancer remains challenging despite many advances in therapeutic options. Platinum-based drugs have been used to treat ovarian cancer since the late 1970s. Most ovarian cancer patients respond well to platinum-based drugs at the beginning of the treatment, but they often become resistant to the drugs quickly.
To optimize the treatment of ovarian cancer, The Wistar Institute scientists looked at another class of drugs called BET inhibitors. They found that a combination of BET inhibitors and platinum-based drugs can reduce tumor drug resistance. The findings, published in Cancer Research, indicated that BET inhibitors can improve the effectiveness of platinum-based drugs and thus enhance the survival of experimental mice.
It has already been known that cancer stem cells are responsible for drug resistance. Specifically, the enzyme ALDH plays a role in tumor drug resistance. Inhibiting this enzyme can sensitize ovarian cancer cells to therapeutic agents. A platinum-based drug called cisplatin is known to promote the activity of ALDH, resulting in cisplatin resistance.
Wistar researchers found that BET inhibitors are capable of inhibiting ALDH in epithelial ovarian cancer cells. They also discovered that BRD4 -- one of the proteins that are inhibited by BET inhibiting drugs -- appears to regulate ALDH activity. In addition, the protein BRD4 is over-abundant in epithelial ovarian cancer.
The researchers then tested cisplatin and an experimental BET inhibitor called JQ1 in mice that had epithelial ovarian cancer-derived tumor cells. Mice that received both cisplatin and JQ1 survived much longer than mice that only got cisplatin. Furthermore, the combination of cisplatin and JQ1 obviously delayed the outgrowth of tumors.
In sum, the study shows that BET inhibitors such as JQ1 may be used to decrease ALDH activity in epithelial ovarian cancer and thus reduce a tumor’s resistance to platinum-based chemotherapy drugs.
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