Pharmacological drugs under investigation show effect on tumor-initiating cells

December, 13,  2010. Scientists from the Vall d’Hebron Institute of Oncology (VHIO) in Barcelona have discovered markers that identify the cells within the tumor that are responsible for the initiation and recurrence of tumors. They have also shown that drugs under clinical development can eliminate these cells, and therefore minimize recurrence and potential resistance of the tumors to conventional chemotherapy in a study published in Cancer Cell.

The group led by Dr Joan Seoane, ICREA Research Professor at the VHIO, has carried out the research in glioma, the most common malignant brain tumor. The study published today describes how to identify cells with characteristics of stem cells in the interior of the glioma. These cells, known as Glioma initiating cells (GICs), are responsible for initiating the glioma and also for it reappearing after surgical removal.. “It is as if we were talking about a persistent weed”, says Dr. Joan Seoane, “If we cut the weed down, the bulb remains and the weed sprouts again. The bulb represents GICs.” It is very important to understand that tumors are heterogeneous in their interior and not all the cells are equally malignant. Identification of the malignant cells is fundamental for designing new therapies.

The malignant cells express high levels of CD44 and Id1 proteins. “This could have repercussions for many treatments. If we can identify and mark the cells that cause recurrence, we can identify which treatments eliminate them and which don’t,” explains Dr. Seoane. The group has also demonstrated that inhibitors of the hormone TGF-beta eliminate the malignant cells.   “Our study identifies the bulbs, where they are and which drug is effective against them,” says Dr. Seoane. 

This finding has also been tested in mice that reproduce the patient’s tumor after injection with the patient’s tumor cells. Treated cells are injected into a second mouse, which does not develop tumors.   This has also been corroborated with tissue samples from patients that have been treated with the drug. The drugs are currently being tested in a clinical trial at the Research Unit for Molecular Therapy of Cancer “la Caixa” at the VHIO.

Article reference: Anido J., Sáez-Bordenas A., González-Juncà A., Rodón L., Folch G., Carmona M. A., Prieto-Sánchez R. M, Barba I., Martínez-Sáez E. ,Prudkin L., Cuartas I., Raventós C., Martínez-Ricarte F., Poca M. A., García-Dorado D., Lahn M., Yingling J., Rodón J., Sahuquillo J., Baselga J., Seoane J. TGF-b Receptor Inhibitors Target the CD44high/Id1high Glioma-Initiating Cell Population in Human Glioblastoma. Cancer Cell (2010), doi:10.1016/j.ccr.2010.10.023.).

About the Vall d’Hebron Institute of Oncology Foundation (VHIO)
The VHIO is a research center funded by the Autonomous Government of Catalonia, three private non-profit-making foundations and competitive funding. It is built on a model of translational research, combining basic cancer research with clinical studies in the context of a hospital renowned for treatment of oncology patients. The Scientific Director, Josep Baselga, and his team are responsible for the VHIO’s excellent record for patient care, clinical trials and research publications.

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