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CNIO Publications, Year 2016

Scientific Reports

The collaboration between the CNIO and Eli Lilly and Company identifies a new therapeutic target for lung cancer

Madrid, 10 October, 2016

Researchers have discovered a new alteration in lung cancer, which is a step towards personalized treatment of this disease

The anomaly is found in NSD2, an epigenetic protein which is thought to be a driver of specific hematological and solid tumors. It is therefore an interesting target for oncology drug discovery

 The work is published in 'Scientific Reports'

Cancer is a different disease in each patient, and improved treatment demands knowing more about the personal characteristics of each tumor. A CNIO team has discovered a new alteration in lung cancer, and thus a new therapeutic target to develop specific drugs. The finding is therefore a step towards customizing the treatment of lung cancer.

The work, published today in the journal Scientific Reports, has been possible thanks to the collaboration of the CNIO with Lilly.

The reported alteration affects a protein called NSD2. The research team, led by Maria Jose Barrero, has found that alterations in NSD2 act together with the already known RAS oncogene to promote the proliferation of lung cancer cells. It is actually a combination of two alterations, in NSD2 and the RAS oncogene, that promotes tumor growth.

In this way, the researchers have further subdivided the “RAS mutant” subtype of lung cancer.

A "NEW MOLECULAR DEFINITION” FOR LUNG CANCER

"We have identified a new molecular subtype of lung tumors," says Barrero. "Among tumors with mutations in RAS we have defined a subgroup in which NSD2 is overexpressed; that is to say, it is in excess amounts in the tumor."

The new “molecular definition” is important, because this variant of lung cancer cannot be fought only with drugs against oncogene RAS: "It is necessary to act against RAS and possibly also counteract the overexpression of NSD2," Barrero said.

At present, there are still no drugs targeting NSD2, but this protein has already been of interest for the pharmaceutical industry since it is known to be mutated in certain hematologic malignancies and overexpressed in several solid tumors. However, as the researchers explain in their paper, "Its contribution to the biology of solid tumors is still not well understood and will require additional research." For all these reasons, the CNIO group focused from the beginning in trying to understand the role of NSD2 in lung cancer. The work has been performed using cell lines of this type of cancer only, but researchers believe that overexpression of NSD2 could drive other tumors, acting in conjunction with RAS or other oncogenes. One of the next steps of the research is to "identify tumors and cell lines dependent on NSD2", as explained in Scientific Reports.

This is the first result of an Epigenetics collaboration between Lilly and the CNIO, a unique initiative in the Spanish biomedical research landscape that began three years ago. The CNIO-Lilly Epigenetics Laboratory, integrated by two researchers and two technicians, makes public the highlights of their research.

Reference article:

NSD2 contributes to oncogenic RAS-driven transcription in lung cancer cells through long-range epigenetic activation. Verónica García-Carpizo, Jacinto Sarmentero, Bomie Han, Osvaldo Graña, Sergio Ruiz-Llorente, David G. Pisano, Manuel Serrano, Harold B. Brooks , Robert M. Campbell & Maria J. Barrero. Scientific reports (2016). DOI: 10.1038/srep32952


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