(Press-News.org) Researchers at University of California, San Diego School of Medicine have established the safety and dosing of a new drug for treating blood cancers. The findings are published online July 27 in The Lancet Haematology.
The drug is a small molecule inhibitor that suppresses the activity of a signaling pathway believed to contribute to a variety of blood cancers' eventual resistance to standard chemotherapy treatments.
More specifically, preclinical research, funded in part by the California Institute for Regenerative Medicine (CIRM), has shown that the drug coaxes dormant cancer stem cells, residing in the bone marrow, to begin differentiating and exit into the blood stream where they can be destroyed by chemotherapy agents targeting dividing cells.
"This drug gets that unwanted house guests to leave and never come back," said the study's senior author Catriona Jamieson, MD, PhD, an associate professor of medicine and chief of the Division of Regenerative Medicine in the School of Medicine. "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."
The drug's name is PF-04449913, Pfizer's alphanumeric designation for an investigational medication. PF-04449913 targets the sonic Hedgehog signaling pathway, one of the key regulators of vertebrate embryonic development and the regeneration of adult tissues.
For the first-in-human study, funded in large part by Pfizer, 47 adults with blood and marrow cancer received escalating daily doses of the drug in 28-day cycles. Treatment cycles were repeated until a participant experienced unacceptable adverse effects without evidence of clinical improvement. Those who showed clinical activity from the drug, without serious side-effects, received additional treatment cycles. The phase 1 clinical trial was conducted at three medical centers in the United States, including UC San Diego Health, and one center in Italy from 2010 to 2012.
Of the 47 study participants, 28 individuals, or 60 percent of the group, experienced treatment-related problems. Adverse effects were severe, however, in only three people. The drug elicited clinical activity sufficient to establish proof-of-concept for the treatment in 23 individuals, or nearly half the study participants.
Given the promising results, the drug's efficacy as a treatment for different types of blood cancer is now being investigated in five phase II clinical trials, three of which are currently recruiting participants at UC San Diego Health.
"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," Jamieson said. "It's all about reducing the burden of disease by intervening early."
"This new drug highlights the value of understanding stem cell signaling pathways as a tool for developing truly novel approaches for improving human health," said C. Randal Mills, PhD, president and CEO of CIRM, California's stem cell agency.
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Co-authors include Giovanni Martinelli, Cristina Papayannidis, and Michele Baccarani, University of Bologna, Italy; Vivian G Oehler, and Jerald Radich, Fred Hutchinson Cancer Research Center, Seattle; Rachel Courtney, M Naveed Shaik, Karen R McLachlan, Xianxian Zheng, and Wendy J Levin, Pfizer Oncology, La Jolla; Xiaoxi Zhang, Pfizer Oncology, New York; Ashleigh O'Connell, Pfizer Oncology, Collegeville; and Hagop M Kantarjian, and Jorge E Cortes, MD Anderson Cancer Center, Houston.
In addition to funding from CIRM and Pfizer, the European Leukemia Net also provided support for the study.
Researchers at Children's Hospital Los Angeles and The Saban Research Institute of CHLA have created a dynamic functional mouse model for lung injury repair, a tool that will help scientists explain the origins of lung disease and provide a system by which new therapies can be identified and tested. Their findings have been published online by the American Journal of Respiratory Cell and Molecular Biology.
The novel model used targeted Type 2 Alveolar Epithelial cells (AEC2), which line the small sac-like cavities of the lung and are thought to be responsible for injury ...
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The Tyrannosaurus rex and its fellow theropod dinosaurs that rampage across the screen in movies like Jurassic World were successful predators partly due to a unique, deeply serrated tooth structure that allowed them to easily tear through the flesh and bone of other dinosaurs, says new research from the University of Toronto Mississauga (UTM).
The research, published in the journal Scientific Reports, was conducted by Kirstin Brink, a post-doctoral researcher in the Department of Biology at UTM; Professor Robert Reisz of the Department of Biology and the UTM vice-principal ...
Diseases like Alzheimer's are caused when proteins aggregate and clump together. In a world first, EPFL scientists have successfully distinguished between the disease-causing aggregation forms of proteins. The finding can help change pharmaceutical treatment of neurodegenerative diseases.
Because of our increasing lifespan, diseases like Parkinson's, Huntington's and Alzheimer's are on the rise. They are caused when certain proteins misfold and aggregate together, forming clumps that damage neurons in the brain and spinal cord. This aggregation evolves progressively through ...
PITTSBURGH, July 28, 2015 - By studying the yeast used in beer- and bread-making, researchers at the University of Pittsburgh School of Medicine have uncovered the mechanism by which ancient proteins repair DNA damage and how their dysfunction could lead to the development of tumors. The findings, published online today in Nature Communications, could lead to new ways to tailor cancer therapies.
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DURHAM, N.C. -- The light-sensing molecules that tell plants whether to germinate, when to flower and which direction to grow were inherited millions of years ago from ancient algae, finds a new study from Duke University.
The findings are some of the strongest evidence yet refuting the prevailing idea that the ancestors of early plants got the red light sensors that helped them move from water to land by engulfing light-sensing bacteria, the researchers say.
The results appear online in Nature Communications.
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Adding omega-3 fatty acids to anti-tumor medications may improve treatment response and quality of life for cancer patients according to a new study by researchers at the University Hospitals of Leicester in the United Kingdom.
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Babies born very premature or severely underweight are at heightened risk of becoming introverted, neurotic, and risk averse as adults, indicates research published online in the Archives of Disease in Childhood (Fetal & Neonatal Edition).
This personality profile may help to explain the higher rates of career and relationship difficulties experienced by this group as adults, suggest the researchers.
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