Focus on Research: 3 New DIPG Abstract This Week!

One of the frustrating things about medical research is the delay between when research is presented at a scientific meeting and when it actually gets to publication.   Unfortunately, sometimes the gap is more than a year.   For this reason, I trawl around the meeting abstracts which might have potential.    One such meeting is the American Association of Cancer Research (AACR) concluding it's five-day Annual Meeting tomorrow.    I am thrilled to report there are DIPG presentations at this meeting.

Here are the citations for the three presented abstracts:

1)  Nathalene Truffaux, Ludivine Le Dret, Stephanie Puget, Gilles Vassal, Birgit Geoerger, Jacques Grill.
Activity of dasatinib and potential escape mechanisms in diffuse intrinsic pontine glioma (DIPG) models
 In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; 2013 {Abstract 2763}

2)  Sridevi Yadavilli, Madhuri Kambhampati, Oren J. Becher, Tobey MacDonald, Ravi Bellamkonda, Roger J. Packer, Javad Nazarian. 
NG2 upregulation and its defective asymmetric distribution in pediatric brainstem glioma and diffuse intrinsic pontine glioma
In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; 2013. {Abstract 5004}

3)  Marianne Hutt, Wendy Goldstein, Javad Nazarian, Antoinette Price, Kah Jing Lim, Katherine Warren, Howard Chang, Charles Eberhart, Eric Raabe.
Targeting the Notch and mTOR pathways in diffuse intrinsic pontine glioma
In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; 2013.  {Abstract 5049}

The first abstract is from the French researchers that have pioneered the way for biopsies.  The second is from National Children's in DC, Duke and Emory/Georgia Institute of Technology.  The third is from the Mid Atlantic DIPG Consortium (MADC).  The MADC abstract appears to be an extension of the abstract we highlighted here on March 23this year.

As the abstracts are meant for a group of researchers, they are most definitely highly scientific.  Here is one thing to take away-  it is possible to establish cell lines from freshly biopsied DIPG material.   The French group has been able to establish 12 lines in this way!  

Be On The Lookout- Notch Pathway and DIPG

With the lag time between presentation at a meeting and publications often times things can just slip under the radar.   For me, this was certainly true of this American Association for Cancer Research abstract presented last year in Philadelphia- "High-level activation of the Notch pathway in diffuse intrinsic pontine glioma".  The title doesn't immediately excite me.  However, packed in this short abstract is a number of significant advancements in DIPG research.

1) MADC, the Mid-Atlantic DIPG Consortium, brought three geographically tied institutions together to fight DIPG.   Johns Hopkins, Children's National Medical Center and the National Institutes of Health-Pediatric Oncology Branch agreed to share DIPG tumor material that had been obtained through timely autopsy donation.

2) From a fresh tissue specimen, the researchers were able to establish a cell line- JHH-DIPG1.   The cell line was evaluated for the Notch pathway as this is known to occur in other aggressive brain tumors. JHH-DIPG1 showed a high level of  Notch pathway activation.  

3) From the cell line, a xenograft animal model was also developed.

So.... what makes this significant?  Well,

First, it is very difficult for any one institution to have enough DIPG tissue for research.   I see these type of collaborative efforts key to being able to crack the code of DIPG.

Secondly, it continues to show that parents will donate tumor after death to try to make a difference in this horrendous disease.    It shows that Stanford was not a fluke.  Cell lines and animal models can be developed for DIPG.

Thirdly, it brings DIPG more on par with other brain tumor and cancer researchers.  We now have cell lines and animal models (not only at Hopkins but also elsewhere).  Without these, research seemed at a standstill.

Finally, there are actual Notch agents that are available!  The pediatric phase 1 with the gamma-secretase inhibitor RO4929097 has already closed because it has reached its enrollment.  We are now just waiting for results.   The research here could be a basis for starting a clinical trial for DIPG with an agent- or at least being able to do more pre-clinical work with an appropriate model.   

References:
AACR Notch Abstract-
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=5eccf257-1e78-44ad-a11d-0cb24040c222&cKey=c6e7a032-873e-4aea-a5af-1b3374b5b338&mKey=%7B2D8C569E-B72C-4E7D-AB3B-070BEC7EB280%7D

Gamma-secretase inhibitor RO4929097 in treating young patients with relapsed or refractory solid tumors, CNS tumors, lymphoma or T-Cell Leukemia
http://clinicaltrials.gov/ct2/show/NCT01088763?term=Notch+brain+tumor&rank=7