New Strategy for Blocking Oncogene

New Strategy for Blocking Oncogene Recently, a research team in the University of Michigan proposed a new way to block one of the most common cancer-causing gene without causing side effects. This study was published in Immunity recently.

Notch gene plays a role in many types of cancers. It is the most common cancer-causing gene in the T-cell acute lymphoblastic leukemia. About 60% of children and adult patients are carrying the Notch gene mutation. However, drugs designed to block Notch has caused serious side effects such as severe diarrhea or skin cancer.

Now, a research team from the University of Michigan provides a potential new target for the block of Notch oncogene with no toxic effects.

The researchers found that a protein, called Zmiz1 can be combined with Notch and together trigger the oncogenic function of this gene. But Zmiz1 does not affect the function of normal, healthy Notch.

Dr. Mark Chiang points out: “Notch has a control over carcinogenic gene, but it is also important health. Challenge is that knockout carcinogenic function but retain its normal function.”

Chiang added: “If you separate Zmizi1 with Notch, the cancer cells will die. Zmiz1 seemed to open the carcinogenic function of Notch selectively.”

When the Zmiz1 is deleted, the mice live longer. And the wight is normal, no serious side effects.

“Our goal is to develop a drug right between Notch and Zmiz1, so to break the binding between the two. We believe this can block the oncogenic pathways of Notch without no serious side effect.”

Though most of the T-cell leukemia in children can be cured, about 20 percent of them will relapse. Those children are faced with a severe prognosis. So far, they haven’t a targeted treatment.

Chiang said: “We need to develop a method for the treatment of Notch to help children with cancer recurrence, with less toxicity or long-term effects. Current therapies are often effective but it may pay heavy effect in the long run.”

Of course, more researches are needed to reach this point. Chiang and his colleagues are planning to use X-ray crystallography to produce three dimensional images of Notch and Zmiz1, trying to understand how they stick together.