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

Inspiring Kids- Calle and Hope for Caroline Inc

Five year old Caroline Cronk was just diagnosed with a DIPG in November 2012. Yet in that short time Caroline (fondly called Calle), her family and her friends have worked hard to shine as much of a spotlight on DIPG as possible.  Just yesterday, March 2, the Boston Globe updated there remarkable story.
http://www.boston.com/news/local/massachusetts/2013/03/03/when-cancer-strikes-their-child-norwell-couple-fight-back-with-prayer-fund-raisers-and-hope/sT30txaUToDf2PgyGBCb2I/story-1.html

Her story started as so many other kids have.   Calle started having fatigue- then balance issues.  A head tilt and squinting of the eyes were noticed.  Her face became paralyzed on a side.  A walnut sized mass was found in the pons.

What is remarkable is that they have not just focused there energy inward toward there family but have also started a new DIPG foundation- Hope for Caroline Inc.  There are several upcoming fundraisers including a pancake breakfast next weekend and Calle's Miracle Run a month from now.  However, they have already made their mark on DIPG research by contributing $100,000 on Feburary 8th to the Dana Farber lead research trial utilizing brain-stem biopsies "to trace signals driving the tumor and provide targeted treatments".

This trial has been funded by a coalition of private funds from various sources.   Without these foundations helping to make a difference this trial very likely would not be possible.

This novel trial is hoped to completely transform our understanding of DIPG.   The trial is listed to be currently open at 6 institutions in the US- Seattle Children's, Hopkins, Cook Children's in Texas, Lurie Children's in Chicago, Washington University in St. Louis and Dana Farber in Boston.  There are several other collaborating institutions in this trial so there is hope that other hospitals will have this trial open in the future.  

Best Wishes to Calle!
Best of hope to Hope for Caroline- keep up the great work!


References-
Hope for Caroline, Inc http://hopeforcaroline.org/

Clinical Trial- Molecularly Determined Treatment of Diffuse Intrinsic Pontine Gliomas (DIPG) http://clinicaltrials.gov/ct2/show/NCT01182350?term=DIPG&rank=5

5-year-old Calle Cronk, her family fight rare illness  http://www.bostonglobe.com/metro/2013/02/08/young-calle-cronk-and-her-family-face-unknowns-brain-tumor/dylgSGNkCmuVUHPTcB64zM/story.html

Story of sick Norwell girl goes national; social media attract support

 http://www.bostonglobe.com/metro/2013/02/08/young-calle-cronk-and-her-family-face-unknowns-brain-tumor/dylgSGNkCmuVUHPTcB64zM/story.html

Understanding the Journey, A Parent's Guide to DIPG

Here is a excellent resource for anyone who really wants to understand the issues surrounding DIPG kids- from day to day treatment to current research.   Each chapter is written by leading pediatric brain tumor experts such as Mark Souweidane, Michelle Monje, Ken Cohen, Mark Kieran, George Jallo and many others.  The chapters are followed by dozens of personal stories from parents who have walked this path.

The book was developed by the American Childhood Cancer Organization (formerly known as Candlelighter's Childhood Cancer Foundation).   The book is available free to families who join ACCO-

http://www.acco.org/Information/Resources/Books.aspx  

(page down to the 4th book which has a child walking down a road on the cover).  

This is a worthwhile addition for anyone dealing with DIPG.  

Thanks ACCO! 

Book Description from ACCO site-

a 368 page comprehensive resource that guides the family whose child has been diagnosed with a diffuse intrinsic pontine glioma through this difficult diagnosis. Chapters are written by pediatric neuro-oncology experts and cover all aspects of treating a child with a DIPG including: diagnosis, imaging, pontine function and anatomy, steroid treatment, radiation therapy, radiosensitizers, surgery, chemotherapy and biologics. Helpful chapters on loss of communication and caring for the child at home provide practical advice. Research chapters focused on animal models of DIPG, stem cell research, vaccine research, convection enhanced delivery and genomic research provide hope for a brighter future. The final chapters on organ and tissue donation as well as integrating palliative care answer the questions that families ask at their child's end of life. The book includes 164 parent stories that provide personal insight to the DIPG journey.

Inspiring Kids- Teen with DIPG in the News

Just a few years ago it was rare to hear DIPG in the news- maybe brain cancer or brainstem glioma  but not  DIPG.   Now though there is growing awareness-- and the stories not only use the initials but actually explain the bad and ugly of this tumor.

Here is a great example--  a story about a teen from Utah being treated at St. Jude that truly highlights the changes in awareness.   There are the devastating facts about DIPG.   There is also the face and spirit of a determined teen who “can do hard things”.

This article is associated with a six minute news video.

http://www.ksl.com/?sid=24061857&nid=148&s_cid=rss-extlink

Her blog has received over a quarter million visitors.

Inspiring.