Israeli scientists have isolated cancer stem cells that lead to the growth of a type of tumor typically found in the kidneys of young children. The team at Sheba Medical Center, Tel Hashomer has also developed a new therapeutic approach that could eventually provide an alternative to the often damaging chemotherapy now used on children with renal cancer.
The study, published online in EMBO Molecular Medicine, was led by Prof. Benjamin Dekel, head of the Pediatric Stem Cell Research Institute at the Edmond and Lili Safra Children's Hospital at Sheba.
A small sub-set of cancer cells are primarily responsible for the creation and spread of tumors. In recent years, researchers have been developing treatments designed to target these cancer stem cells, or CSCs as they are known, in various forms of the disease.
In the paper, Dekel and his team described how, for the first time, they succeeded in identifying CSCs in children suffering from Wilms' tumors, the most common form of pediatric kidney tumors. This tumor occurs at a rate of 0.8 per 10,000 children and has a tendency to spread and develop metastases. The researchers also reported on an innovative therapy specifically targeting these cells.
Identifying cancer stem cells required establishing a unique system for growing human renal tumors in mice. "We took tissue from pediatric patients and grafted them into genetically engineered mice. We identified the cancer stems cells in these tumors and showed that only the CSCs and not the other cancer cells led to the development of new tumors upon grafting into additional mice," explained Dekel, who is also a senior physician at the Sheba Medical Center and the Sackler School of Medicine at Tel Aviv University.
The team then identified molecules on the surface of these cells and developed an antibody drug targeting one of these molecules, which successfully eliminated a group of cancer stem cells.
"The targeted elimination of CSCs fueling the tumor led to shrinkage and in some cases the complete eradication of the tumors we induced in mice without causing any toxic side effects," Dekel explained. The antibody is currently being tested in clinical trials with adult cancer patients and, if approved, may also be tested on children.
The results are likely to affect the future of specific therapy development for kidney cancer, such as Wilms' tumors. "The discovery may help people in the relatively near future. An antibody targeting cancer stem cells could ...make the heavy use of chemotherapy in children suffering from renal cancer redundant, thereby lessening the side effects of treatment that sometimes lasts years," said Dekel.
Conventional chemotherapy is toxic to all cells in the body and if given to children may lead to the development of secondary cancers when they are older.
The research team at the Pediatric Stem Cell Research Institute at Sheba Medical Center consisted of Naomi Pode-Shakked, a student at Tel Aviv University who developed the model for identifying the cells, Rachel Shukrun, Dr. Michal Mark-Danieli and Dr. Orit Harari-Steinberg, as well as Prof. Yoram Mor from the urology department and Dr. Edward Fridman from the pathology institute.
Currently the Pediatric Stem Cell Research Institute at Sheba Medical Center is continuing to identify cancer stem cells in other pediatric tumors to find ways of targeting them.
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