Two UC Irvine scientists have rocked the cancer research community with a discovery suggesting that a drug already on the market might be able to eradicate cancerous cells in chronic myeloid leukemia (CML) patients. Associate Professors Natalia Komarova and Dominik Wodarz showed how the drug Imatinib can eventually rid the body of cancerous cells if it is taken for a prolonged period of time.
Imatinib has long been considered one of the best treatments for CML because, unlike most other treatments, Imatinib specifically targets cancerous cells. It works by turning off the tyrosine kinase enzyme, which is responsible for allowing CML cells to evade normal cell death and subsequently multiply at unnatural rates.
Although this drug is effective while administered, CML cells often return after treatment has ceased. Some scientists think this occurs because Imatinib kills normal CML cells but then fails to destroy the CML stem cells.
However, Komarova and Wodarz suggest that the ineffectiveness of Imatinib against CML stem cells is because the drug can only destroy stem cells that are active. When the stem cells enter an inactive stage known as quiescence, they become invisible to Imatinib and thus survive. Upon waking, they are able to resume normal activity and cause cancer to spread once again.
As a result, the two scientists created a model that considers this information and uses it to come up with a formula for treating each particular case of CML.
‘The model helps calculate how long it takes to eradicate cancer by using small molecular inhibitors or other targeted drugs like Imatinib,’ Komarova said.
While these findings are promising, they cannot be used in the actual treatment of CML yet. ‘More experimental work has to be done,’ Komarova said. Much of this work involves finding out certain details, or parameters, regarding quiescence.
‘The most important ones are how often cancerous cells fall asleep and how quickly they wake up,’ Komarova said. ‘If they can measure this, then we can plug those values in the formula, and this will give a prediction of how long treatment can possibly take.’
This is not Komarova and Wodarz’s first collaborative project. In 2005, they co-authored the book ‘Computational Biology of Cancer: Lecture Notes and Mathematical Modeling.’ Additionally, they have done research exploring drug resistance as it relates to cancer.
Both scientists have studied in various parts of the world and have worked elsewhere before coming to UCI. Komarova was born in Moscow, Russia. She completed her undergraduate studies at Moscow State University, then came to the United States and received her Ph.D. in applied mathematics at the University of Arizona.
Komarova did her postdoctoral appointment at the University of Warick in England. Then she worked at the Institute for Advanced Studies in Princeton. Her first faculty appointment was at Rutgers University, where she was an assistant professor in the math department. Komarova is currently an associate professor of mathematics at UCI.
Wodarz was born in Bonn-Bad Godesberg, Germany. He completed his undergraduate work in the Department of Biology at Imperial College, London, then received his Doctorate of Philosophy from the University of Oxford. He was a member of the Institute for Advanced Studies in Princeton and an associate member of the Fred Hutchinson Cancer Research Center in Seattle, Wash. He then came to UCI, where he is currently a tenured associate professor in the Department of Ecology and Evolution.