Nov. 13, 2012 Cancers arise when a normal cell acquires a mutation in a gene that regulates cellular growth or survival. But the particular cell this mutation happens in -- the cell of origin -- can have an enormous impact on the behavior of the tumor, and on the strategies used to treat it.
Robert Wechsler-Reya, Ph.D., professor and director of the Tumor Development Program in Sanford-Burnham's NCI-designated Cancer Center, and his team study medulloblastoma, the most common malignant brain cancer in children. A few years ago, they made an important discovery: medulloblastoma can originate from one of two cell types: 1) stem cells, which can make all the different cell types in the brain or 2) neuronal progenitor cells, which can only make neurons.
Stem cells and progenitor cells are regulated by different growth factors. So, Wechsler-Reya thought, maybe the tumors arising from these cells respond differently to different therapies…
In a study published recently in the journal Oncogene, he and his team show that this is indeed the case. They looked at one growth factor in particular -- basic fibroblast growth factor (bFGF) -- and found that while it induces stem cell growth, it also inhibits neuronal progenitor cell growth.
What's more, the researchers discovered that bFGF also blocks the growth of tumors that originate from progenitors. When they treated a mouse model of medulloblastoma with bFGF, it dramatically inhibited tumor growth.
Although bFGF itself can't be used as a drug (it would cause too many off-target effects), this study suggests that molecules like it might be used to treat medulloblastoma -- but only for tumors that have the appropriate origins.
"Medulloblastomas are not all alike, and the same is true for cancers of the breast, prostate and other tissues. It's critical for us to figure out how tumors differ from one another, so we can find ways to personalize cancer diagnosis and come up with treatments that are more effective and less harmful," Wechsler-Reya says.
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- B A Emmenegger, E I Hwang, C Moore, S L Markant, S N Brun, J W Dutton, T-A Read, M P Fogarty, A R Singh, D L Durden, C Yang, W L McKeehan, R J Wechsler-Reya. Distinct roles for fibroblast growth factor signaling in cerebellar development and medulloblastoma. Oncogene, 2012; DOI: 10.1038/onc.2012.440
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