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FSB Laboratory-CNIO

Massimo Squatrito

The Seve Ballesteros Foundation has an international presence operating both in the United Kingdom and Spain. In the UK, it has worked together with Cancer Research UK, the largest charity dedicated to fighting cancer through research.  In Spain, the Seve Ballesteros Foundation supports the National Cancer Research Centre by way of the Seve Ballesteros Foundation Laboratory. Since it started in 2011, the Foundation has supported financially this research with 700.000 euros.


Massimo Squatrito, FSB-CNIO program update


Laboratorio FSB-CNIO

The Seve Ballesteros Foundation Laboratory-CNIO focuses its efforts in developing a wider knowledge of the different types of cancer that might affect the central nervous system. Achieving a better understanding of the events leading to cancer development and discovering molecular mechanisms could provide a basis for novel therapies. Thus, the new lab focuses it’s work on:

  • Discovering molecular mechanisms related to the birth or growth of tumours in the central nervous system.
  • Identification of markers orientated to a better and more efficient tumour diagnosis and outlook in the central nervous system.
  • Development of new drugs based on specific targets.
  • Implementation of pharmacological and biomarker studies that have an effective clinical application in early stages with new drugs.
  • Development of clinical research in early stages with new drugs.
  • Collaboration and interaction between basic and clinical research to obtain therapeutic progress in this kind of tumours and develop training programmes.
  • The researchers approach to patients and the homogenisation of the origin of the tumour samples.
  • The search and assessment of new technologies that will enable early detection of this kind of tumours and treatment once detected.
  • Improvements in the patient selection that will benefit from this therapy, search for new toxic drugs and adapting the different drug combinations to genetic and protein features of each tumour in order to increase survival rates.

This project has incorporated Dr. Massimo Squatrito from the Sloan-Kettering Memorial Institute in New York, one of the most prestigious cancer centres in the world. Thanks to the CNIO and the support of so many individuals, the Seve Ballesteros Foundation has reached the aim of increasing scientific and clinical research in Spain with scientists from world renowned research centres coming to Spain to carry out their projects. The Group studies how brain tumours, mainly glioblastomas and medulloblastomas, develop and how they respond to therapy.


Malignant brain tumors represent about 3% of the known cancers and every year about 100,000 new cases are diagnosed worldwide. Glioblastoma is the most common and lethal primary central nervous system tumour in the adults. A decade of studies has underlined the complexity of the glioma genome, however, the functional significance of the vast majority of the genetic alterations remains elusive.

The Seve Ballesteros Foundation-CNIO Brain Tumor Group, headed by Massimo Squatrito, in collaboration with the laboratory of Ingo Mellinghoff at the Memorial Sloan-Kettering Cancer Center in New York , has uncovered a novel mechanism that contributes to prevent glioblastoma development.  


 

Massimo Squatrito, head of the group of Brain Tumours at the Nacional Cancer Research Centre


The epidermal growth factor receptor plays a critical role in normal development and in human cancer. EGFR is one of the first receptor tyrosine kinases linked to human cancer and represents an important drug target in oncology. Aberrant activation of EGFR in cancer stimulates tumour growth and is primarily attributed to increased gene copy numbers or gain-of-function mutations. However, it can also result from defects in EGFR feedback regulation.

Squatrito and colleagues have discovered a novel layer of complexity in the regulation of EGFR. They have identified a previously uncharacterized protein – –, as a modulator of EGFR expression. The authors show that RanBP6 is an importin family member that is lost in a subset of glioblastoma patients. Silencing of RanBP6 promoted glioma growth in glioma mouse model, by upregulating EGFR expression.

The results provide an example of EGFR deregulation in cancer through silencing of components of the nuclear import pathway. The investigators have identified a new link between the nuclear transport pathway and key cancer signaling pathways which warrant further study as inhibitors targeting nuclear transporters enter clinical evaluation as cancer therapeutics.

Seve Ballesteros Foundation in partnership with Cancer Research UK