Finding the Source of Cancer Recurrence


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Prof. Ehud Shapiro, Dr. Rivka Adar, Adam Spiro and Noa Chapal-Ilani



Long after a cancer has been beaten into remission, it can return. New research led by Institute scientists recently provided strong evidence that in leukemia, at least, this is due to cancer stem cells – cells that divide slowly and are thus immune to the attacks of the chemotherapy drugs that target only the rapidly dividing cells. Nonetheless, they are capable of generating new cancer cells that divide rapidly.

In recent years, scientists have been finding signs of these cancer stem cells. Such cells are thought to hide in the body long after the chemotherapy has eradicated the main cancer growth, eventually giving rise to new cancer. But it has been unclear whether these cells really are the source of renewed cancer or whether the new growth simply comes from a small population of “ordinary” cancer cells that managed by chance to survive the treatment.

Approaching the issue with a method for reconstructing cell lineage trees that he and his group have developed over the past few years, Prof. Ehud Shapiro and his team in the Biological Chemistry and the Applied Mathematics and Computer Sciences Departments worked with scientists and doctors from Rambam Medical Center and the Technion, in Haifa. In the method, a comparison of the mutations that cells have accumulated over the course of cell division enables researchers to map out the cells' “familial” relations and determine how far back they share a common ancestor.
Leukemia cells. Image: Wikimedia Commons, NIH
The lineage tree was based on two sets of blood samples: The first taken from leukemia patients right after the disease was diagnosed and the second from those patients in whom the cancer had returned following chemotherapy. The lineage tree showed that, at least in some of the patients, the source of the renewed cancer was not ordinary cancer cells from the earlier bout, but rather cells that were very close to the base of the cancer lineage tree. In other words, the cancer arose from cells that divide very slowly – cancer stem cells that were immune to the attacks of the chemotherapy drugs yet were capable of recreating a population of rapidly dividing cancer cells.

Shapiro: “Our results suggest that to completely eliminate recurrent leukemia, we must look for a treatment that will not only destroy the rapidly dividing cells but also target the cancer stem cells that are resistant to conventional treatment.”

Participating in the research were Dr. Liran Shlush of the Technion Faculty of Medicine and the Rambam Healthcare Campus; Noa Chapal-Ilani and Dr. Rivka Adar of the Weizmann Institute; Prof. Karl Skorecki of the Technion; Tsila Zuckerman of the Rambam Healthcare Campus; Prof. Clara D. Bloomfield of Ohio State University; and additional scientists.
Prof. Ehud Shapiro's research is supported by the Paul Sparr Foundation;Miel de Botton,UK;the Carolito Stiftung; and the European Research Council. Prof. Shapiro is the incumbent of the Harry Weinrebe Professorial Chair of Computer Science and Biology.