New blood cancer drug reaches cells hiding in bone marrow …

Posted: August 2, 2015 at 7:41 am

SAN DIEGO, July 28 (UPI) -- A new drug aimed at dormant cancer stem cells that hide in the hypoxic zones of bone marrow, where most drugs can't reach, is currently entering 5 Phase II clinical trials after it was shown to make blood cancer treatment more effective.

Researchers in a Phase I clinical trial, the results of which are published in The Lancet Haematology, found that the drug vismodegib was effective against three types of blood cancer -- refractory or resistant myeloid leukemia, myelodysplastic syndrome and myelofibrosis.

Vismodegib inhibits the Hedgehog signaling pathway, which is essential to both vertebrate embryonic development and has been implicated in the development of some cancers. The drug, trade name Erivedge, is already approved in the U.S. and Europe for treatment of metastatic or locally advanced basal cell carcinoma.

"Our hope is that this drug will enable more effective treatment to begin earlier and that with earlier intervention, we can alter the course of disease and remove the need for, or improve the chances of success with, bone marrow transplantation," said Dr. Catriona Jamieson, chief of the Division of Regenerative Medicine in the School of Medicine at the University of California San Diego, in a press release. "It's all about reducing the burden of disease by intervening early."

Preclinical research showed the drug could "coax" dormant cancer stem cells in hypoxic zones to begin differentiating and enter the bloodstream, where they can be attacked by the chemotherapy and the immune system.

In the study, researchers treated 47 adults with blood and marrow cancers with with the drug in 28-day cycles. Treatment cycles were continued with escalating doses until a participant experienced adverse effects with no improvement in their condition. The participants who did not have adverse reactions or serious side effects continued to receive treatment cycles of the drug.

Serious adverse effects were seen in only 3 of the participants, though 60 percent of the group experienced treatment-related problems. Nearly half the people in the study saw positive clinical activity as a result of treatment with vismedogib, the researchers said, and 5 Phase II clinical trials are being scheduled for the drug for use with blood cancer.

"This drug gets that unwanted house guests to leave and never come back," Jamieson said. "It's a significant step forward in treating people with refractory or resistant myeloid leukemia, myelodysplastic syndrome and myelofibrosis. It's a bonus that the drug can be administered as easily as an aspirin, in a single, daily oral tablet."

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