Last week the highly productive, DIPG-focused Netherlands group from VU University Medical Center in Amsterdam put forth another publication which happens to have free full text available!
This research focuses on unravelling the reasons why chemotherapy has not been beneficial against DIPGs and pediatric high-grade gliomas. Are DIPGs just resistant to the agents? Or, is it that something is protecting the cells which causes an otherwise good option to be ineffective?
Part 1- Are glioma cells just resistant to chemotherapy?
To look at the first question, the researchers evaluated 9 pediatric glioma cell lines to eliminate questions of adequate drug delivery. Three of these cell lines were from children with DIPGs and 6 were from supratentorial high grade gliomas. Of the 3 DIPG cell lines, all were of different histologic grades- one GBM, one anaplastic astrocytoma and one diffuse fibrillary asrocytomas. Two of these DIPG cell lines came from children who had not had any treatment. The other cell line came from an autopsy donation done approximately 2 hours after death.
In the screening of these cell lines, several agents had high level of killing tumor cells.
When looking at targeted small molecule agents, these did not fare as well as classical chemotherapies. Some did show some efficacy . The best of these was bortezomib which resulted in more than 50% reduction in cell line surival in 6/9 cell lines. There was little or no effect with erlotinib and everolimus. A hypothesis for this result include that the cell lines were not checked for the targets. If there was a matching of targets and agents the results might have been better. Also since there are multiple messed up pathways combined therapy is generally thought to be needed and a single agents is very unlikely to be effective.
In looking at classic chemotherapy agents, melphalan was the only drug that had significiant toxicity in all cell lines. Interestly that is the exact agent of the new intra-arterial Hopkins DIPG trial!
Other agents that were found to have a signficant effect included doxorubicin, mitoxantrone and BCNU. The next level included etoposide, thiotepa and carboplatin. Carboplatin was of special note since that is what the UK in their CED report.
What this means for DIPG is that DIPG is not necessarily resistant to chemotherapy! Effective drgus might not be the biggest hurdle for a cure for DIPG. It might be getting them to the tumor cells.
This work was funded by KiKa "Stichting Kinderen Kankervrij"- Dutch Children Cancer-free Foundation.
Tomorrow.....
Part 2- Do the efflux transporters protect the glioma cells?
References:
In vitro drug response and efflux transporters associated with drug resistance in pediatric high grade glioma and diffuse intrinsic pontine glioma
PLoS One. 2013 Apr 29;8(4):e61512. doi: 10.1371/journal.pone.0061512. Print 2013.
Free Full Text- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639279/
KiKa Stichting Kinderen Kankervrij- Dutch Children Cancer-free Foundation
http://www.kika.nl/
Monday, May 6, 2013
Sunday, May 5, 2013
More than 2 Million- DC Race for Hope!
Today was the 16th year for the DC Race for Hope. It drew over 11,000 people and raised more than 2 million dollars! The facebook page says that the count is more than 2.3 million and counting. Check out the pictures on their page. It is heartening to see the street with people filled supporting the fight against brain tumors.
One of the teams for the past several years has been David Cook. He is the Season 7 winner of American Idol. He also lost his brother to a 10 year battle with brain cancer. This week he was back on the Idol stage and specific mention was made of his passion for supporting brain tumor research. (Click here to see the video)
In it's history the DC Race for Hope has raised more than 17 million for brain tumor research. The funds go to the National Brain Tumor Society and Accelerated Brain Cancer Cure (ABC2). These foundations are fighting all brain tumors- many kinds and all ages.
Perhaps at one time pediatric brain tumors seemed to be off on their own but not anymore. To me, it definitely seems that DIPG research has matured in the past few years that it has now naturally melded into other glioma research.
I was taken by surprised when ABC2 decided not only to provide funds for the DIPG Preclinical Consortium (initiated at the first DIPG Collaborative Symposium) but also provided strategic advice "to help the research consortium preform DNA (exon) sequencing of all DIPG cell lines, their primary tumor and paired normal DNA via the laboratory of Dr Paul Spellman at OHSU.
And the National Brain Tumor Society sponsored and attended the DIPG Collaborative Symposium. Their Pediatric Research Initiative seems to be exactly what are top priorities for DIPG- molecular profiling and neuordevelopmental biology (gliomagenesis). The National Brain Tumor Society grants in 2010 funded the ground-breaking work DIPG genomic work of both Cynthia Hawkins in Toronto and Suzanne Baker of St. Jude which has reported some of the most exciting results for DIPG- particularly the histone/K27M findings.
Times are changing. Just a few years ago there was no preclinical DIPG research. Now DIPG research has garnered the interest and inclusion from larger brain tumor organizations. DIPG does have alot in common with adult GBMs- particularly poor statistics, invasiveness and the blood brain barrier. The combined efforts with these other organizations seems to be a great thing in fighting DIPG.
Reference:
DC Race for Hope-
http://www.braintumorcommunity.org/site/PageServer?pagename=RFH_DC_Homepage
One of the teams for the past several years has been David Cook. He is the Season 7 winner of American Idol. He also lost his brother to a 10 year battle with brain cancer. This week he was back on the Idol stage and specific mention was made of his passion for supporting brain tumor research. (Click here to see the video)
In it's history the DC Race for Hope has raised more than 17 million for brain tumor research. The funds go to the National Brain Tumor Society and Accelerated Brain Cancer Cure (ABC2). These foundations are fighting all brain tumors- many kinds and all ages.
Perhaps at one time pediatric brain tumors seemed to be off on their own but not anymore. To me, it definitely seems that DIPG research has matured in the past few years that it has now naturally melded into other glioma research.
I was taken by surprised when ABC2 decided not only to provide funds for the DIPG Preclinical Consortium (initiated at the first DIPG Collaborative Symposium) but also provided strategic advice "to help the research consortium preform DNA (exon) sequencing of all DIPG cell lines, their primary tumor and paired normal DNA via the laboratory of Dr Paul Spellman at OHSU.
And the National Brain Tumor Society sponsored and attended the DIPG Collaborative Symposium. Their Pediatric Research Initiative seems to be exactly what are top priorities for DIPG- molecular profiling and neuordevelopmental biology (gliomagenesis). The National Brain Tumor Society grants in 2010 funded the ground-breaking work DIPG genomic work of both Cynthia Hawkins in Toronto and Suzanne Baker of St. Jude which has reported some of the most exciting results for DIPG- particularly the histone/K27M findings.
Times are changing. Just a few years ago there was no preclinical DIPG research. Now DIPG research has garnered the interest and inclusion from larger brain tumor organizations. DIPG does have alot in common with adult GBMs- particularly poor statistics, invasiveness and the blood brain barrier. The combined efforts with these other organizations seems to be a great thing in fighting DIPG.
Reference:
DC Race for Hope-
http://www.braintumorcommunity.org/site/PageServer?pagename=RFH_DC_Homepage
Saturday, May 4, 2013
Dr Souweidane CED Trial on 8th Patient
The Cristian Rivera Foundation, a significant support of the Cornell convection enhanced delivery (CED) trial for newly diagnosed children with DIPG, announced in their April 2013 newsletter that the primary investigator, Dr. Mark Souweidane, is now up to his 8th patient in this trial that opened at the end of 2012.
This is a very exciting, innovative trial for DIPG where a catheter is placed from the top of the head down in to the brainstem. A few weeks after traditional radiation, a radiolabelled antibiody is infused directly in to the pons. Thus, the blood brain barrier is no longer a problem in getting an agent into the tumor.
This is different than other DIPG CED trials in that it uses a radiolabelled antibody. The antibody is
8H9 which has been found in several different tumors. This is linked to 124I which is radioactive. Since radiation has been the only thing that has made a dent in survival statistics the hope seems that this targeted radiation will clean up some of the cancer cells that have thus far been radioresistant with routine radiation.
This trial is the culmination of more than a decade of research utlitizing CED in the brainstem undertaken by Dr Souweidane and his team at Cornell. Below is a video illustrating how CED is performed.
For more information about this trial, about the trial and contact information for Dr. Soweidane click here.
Related Blog Post:
UK Gives CED a Go
http://dipg.blogspot.com/2013/04/uk-gives-ced-go.html
This is a very exciting, innovative trial for DIPG where a catheter is placed from the top of the head down in to the brainstem. A few weeks after traditional radiation, a radiolabelled antibiody is infused directly in to the pons. Thus, the blood brain barrier is no longer a problem in getting an agent into the tumor.
This is different than other DIPG CED trials in that it uses a radiolabelled antibody. The antibody is
8H9 which has been found in several different tumors. This is linked to 124I which is radioactive. Since radiation has been the only thing that has made a dent in survival statistics the hope seems that this targeted radiation will clean up some of the cancer cells that have thus far been radioresistant with routine radiation.
This trial is the culmination of more than a decade of research utlitizing CED in the brainstem undertaken by Dr Souweidane and his team at Cornell. Below is a video illustrating how CED is performed.
Related Blog Post:
UK Gives CED a Go
http://dipg.blogspot.com/2013/04/uk-gives-ced-go.html
Friday, May 3, 2013
DIPG Collaborative
The DIPG Collaborative "is an association of foundations unified with the mission of efficiently funding and inspiring DIPG research in hopes of finding a wider cure for cancer". From The Cure Starts now website it says that the Collaborative Council is to:
1) provide the tools and information to families whose children face the difficult diagnosis of pediatric brain cancer.
2) provide a warm and caring envirnoment to share information, discuss options and support one another.
3) make available accurate and easy to understand information for families that are newly diagnosed.
A major kick off of the DIPG Collaborative was the 2011symposium that brought 13 foundations together with researcher to find substantive ways to research DIPG jointly together. From that meeting several research infrastructure developments occurred which now really allows us to start to unravel DIPG. These included the DIPG Preclinical Consortium, the DIPG Resgistry and the DIPG Genomics Repository.
If one hasn't looked at the Preclinical Consortium, I think it is worth the time as it is impressive. It is less than 4 years from when the first cell line was promulgated in Michelle Monje's lab (from tissue donated by Dylan Jewett). Through the consoritum we now have ten institutions working together on more than 30 cell lines (as well as various animal models) trying to find the best single agents or combinations in those cell lines to be a basis for rapid translation into clinical trials. Every week there is an update on the consortiums work including DNA and RNA analysis. This is fully funded byt the Foundational Leadership Partnters of the DIPG Colaborative.
The DIPG Registry is equally impressive. There is a section for medical professionals including sections on enrollment information and consultations. There is also a section for parents where one can make contact for second opinions and also search for open clinical trials. Parents can make contact with the registry to discuss enrollment- even for children who have died. There already is some specific research in the works.
The DIPG Collaborative Symposium starts today, however, the major work of the DIPG Collaborative for foundations starts tomorrow. The first session is on objectives for the next two years. It would be really interesting to see the direction this collaborative is moving.
There are three levels of support:
Foundational Leadership Partners - The Cure Starts Now, The Cure Starts Now Australia, Jeffrey Thomas Hayden Foundation, Hope for Caroline, Soar with Grace, Reflections of Grace Foundation, The Lyla Nsouli Foundation
Foundation Partners- Smiles for Sophie Forever, Benny World, The Team Julian Foundation
Symposium Sponsors- Max Lacewell Foundation, Love Chloe Foundation, Caroline's Miracle Foundation, Ellie DIPG Research Fund, American Childhood Cancer Organization, Pray Hope Believe Foundation, National Brain Tumor Society, Lurie Children's Hospital of Chicago, Cincinnati Children's Hospital
References:
CSN DIPG Collaborative Council
http://www.thecurestartsnow.org/about/foundation/councils/DIPGcollaborative/
DIPG Collaborative
1) provide the tools and information to families whose children face the difficult diagnosis of pediatric brain cancer.
2) provide a warm and caring envirnoment to share information, discuss options and support one another.
3) make available accurate and easy to understand information for families that are newly diagnosed.
A major kick off of the DIPG Collaborative was the 2011symposium that brought 13 foundations together with researcher to find substantive ways to research DIPG jointly together. From that meeting several research infrastructure developments occurred which now really allows us to start to unravel DIPG. These included the DIPG Preclinical Consortium, the DIPG Resgistry and the DIPG Genomics Repository.
If one hasn't looked at the Preclinical Consortium, I think it is worth the time as it is impressive. It is less than 4 years from when the first cell line was promulgated in Michelle Monje's lab (from tissue donated by Dylan Jewett). Through the consoritum we now have ten institutions working together on more than 30 cell lines (as well as various animal models) trying to find the best single agents or combinations in those cell lines to be a basis for rapid translation into clinical trials. Every week there is an update on the consortiums work including DNA and RNA analysis. This is fully funded byt the Foundational Leadership Partnters of the DIPG Colaborative.
The DIPG Registry is equally impressive. There is a section for medical professionals including sections on enrollment information and consultations. There is also a section for parents where one can make contact for second opinions and also search for open clinical trials. Parents can make contact with the registry to discuss enrollment- even for children who have died. There already is some specific research in the works.
The DIPG Collaborative Symposium starts today, however, the major work of the DIPG Collaborative for foundations starts tomorrow. The first session is on objectives for the next two years. It would be really interesting to see the direction this collaborative is moving.
There are three levels of support:
Foundational Leadership Partners - The Cure Starts Now, The Cure Starts Now Australia, Jeffrey Thomas Hayden Foundation, Hope for Caroline, Soar with Grace, Reflections of Grace Foundation, The Lyla Nsouli Foundation
Foundation Partners- Smiles for Sophie Forever, Benny World, The Team Julian Foundation
Symposium Sponsors- Max Lacewell Foundation, Love Chloe Foundation, Caroline's Miracle Foundation, Ellie DIPG Research Fund, American Childhood Cancer Organization, Pray Hope Believe Foundation, National Brain Tumor Society, Lurie Children's Hospital of Chicago, Cincinnati Children's Hospital
References:
CSN DIPG Collaborative Council
http://www.thecurestartsnow.org/about/foundation/councils/DIPGcollaborative/
DIPG Collaborative
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