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A searchable blog on DIPG research, DIPG news, recent publications, DIPG Foundations, DIPG researchers, clinical trials as well as other issues relating to Diffuse Intrinsic Pontine Tumors- both Diffuse Intrinsic Pontine Gliomas (DIPGs) and Atypical Pontine Lesions (APLs).

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Monday, March 4, 2013

Journal Watch- WEE1 Kinase Inhibition Enhances the Radiation Response of Diffuse Intrinsic Pontine Gliomas.


In the February 12, 2013 edition of the Molecular Cancer Therapy journal, the researchers from the VU University Medical Center in Amsterdam published a new paper using (in mice) using a new agent during radiation- a WEE1 Kinase inhibitor called MK-1775.

So far radiation has been the only therapy to transiently relieve the symptoms in children with DIPG.   One of the hopes has been try try to find ways to increase the effectiveness of radiation.   There have been various trials with radiosensitizer (topetecan,  etanidazole,  motexafin-gadolinium, etc); however,  none have been successful for DIPG.  The researchers looked at a new way to try to enhance radiation's effectiveness.

There are a series of proteins in the cell that control cell division.  One of these protein groups is called WEE1 Kinase and controls the G2 cell-cycle in cell division.   The proteins allow for repair of the damage called by radiation.

These researchers found that WEE1 kinase is expressed more in DIPG tissue than normal tissue.  They theorized that if MEE1 Kinase could be inhibited then the cells would have less ability to recover from radiation.  The great thing is that there is a WEE1 Kinase inhibtor available, MK-1755, and we now have DIPG animal models to test out these novel agents.    They tried this and found that this approach and novel agent might show promise for DIPG.

The interesting thing is that this agent, MK-1755, is currently in clinical trials in adults.  Thus, if this drug shows promise it might be somewhat rapidly translated to pediatric trials for children.

Perhaps something to watch for in the future.

References:
WEE1 Kinase Inhibitor Enhances the Radiation Response of Diffuse Intrinsic Pontine Glioma
http://www.ncbi.nlm.nih.gov/pubmed/23270927