turning cancer on/off with DNA methylation

[Rich66]

Leukemia drug studied in ovarian cancer fight


Posted: January 22, 2009

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Dr. Daniela Matei is a co-leader of experimental and developmental therapeutics at the IU Simon Cancer Center and an associate professor at the Indiana University School of Medicine.
Question: Are there many treatments for ovarian cancer?


Answer: Ovarian cancer is relatively rare, with about 24,000 cases a year in the United States. Unfortunately, it is a uniformly fatal cancer. The vast majority of cancers are diagnosed when they spread beyond ovaries. So it's critical to find better therapies.
The main treatment for ovarian cancer is surgical resection, usually followed by chemotherapy. The mainstay of that treatment is a drug called carboplatin. Most women will respond to carboplatin. The problem is that after treatment, tumors become resistant to carboplatin, which is why most women die.
In some people, this can happen in a month or two and in others it can be years. Those people, where resistance develops in years, can be retreated with carboplatin and there are some other second-line therapies that are not as effective.
Q: Has there been much research into better therapies?
A: There has been work on this for the past couple of decades but unfortunately, there hasn't been a breakthrough.
Q: What are you exploring?
A: We're interested in one of the mechanisms of resistance to carboplatin. What happens is cancer cells learn in time to repair the DNA damage that's caused by chemotherapy. Sometimes they develop mutated proteins to escape the damage created by chemotherapy. Other times they produce proteins in excess that can escape the damage. There are different mechanisms that may be happening in the same person at the same time.
During cancer progression, some protective genes can be silenced, and this silencing can happen through a process of methylation, or chemical modification, of the DNA. This causes the genes to be mute. They are not present and they don't protect the cancer cells.
We use decitabane, a drug for leukemia, which reverses this DNA methylation and allows these protective genes to be present again and make the cancer cells susceptible to chemotherapy.
Q: How does this drug work?
A: We administer it daily for five days and (after two days of no medication) on day eight, we give the patient carboplatin, so we hope that decitabane will break the code of silence and boost the ability of the cancer cells to be again sensitive to chemotherapy. We're focusing on trying to make the cancer cells again naive to chemotherapy as they were initially.
These are for people who have already had chemotherapy, become resistant and now there are no other options.
Q: Who is eligible for this study?
A: We accept all women with ovarian cancer that are willing, and we define resistance as cancer that has recurred within six months of platinum-based treatment. This pretty much comprises the majority of women who have received treatment for ovarian cancer. We are looking for 17 women. We will treat with this as long as it works.