Voices on Pediatric DIPG Biopsy- Mark Kieran MD PhD

Identification of Novel Biologic Targets in the Treatment of 

Newly Diagnosed Diffuse Intrinsic Pontine Glioma

ASCO 2012 Education Session Presentation

The third speaker on the 2012 ASCO session was Mark Kieran from Boston presenting "Identification of Novel Biologic Targets in the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Glioma".  Certainly Dr Kieran has been enduring in his passionate belief that non-treated tissue is going to be critical to the understanding and hopefully cure of DIPG.   He has worked much of the past decade to bring the standard of care for typical pediatric DIPG in line with advancements in neurosurgical techniques and cancer molecular biology research.  The video announcing that DIPG biopsy would be an educational session at 2012 ASCO much have provided a sense of satisfaction that this issue had reached prominence enough to be discussed at a significant cancer meeting. (click here to watch announcement video)

The first video I saw of Dr Kieran discussing this advancements in neurosurgery and cancer molecular biology research that makes DIPG biopsy possible and critical in understanding pediatric DIPGs was back in 2009.   The first international DIPG conference in Barcelona, Spain sponsored by the Alicia Pueyo Foundation included a presentation on this issue.  (click here for video)  The 2012 video shows how far we have come in the DIPG community as well as with cancer molecular biology.

Dr Kieran points out that the understanding DIPG biology is in it's infancy.    Few existing publications are on non-treated (biopsy specimens).  Treatment has the potential of significantly altering the genomics of a tumor.   However, there have been some consistencies:

* P53 loss/mutation is present in a significant number of tumors.

* The RTK-Ras-PI3K-Akt pathway is altered in a number of tumors. 

* PTEN loss might mean that mTOR might be a target.

* Hedgehog-dependent cancer stem cells might be a target.

Regardless of the ultimate biology of DIPG, we can definitely say that DIPG is different from both adult and pediatric high grade gliomas.   Treatment for kids with DIPG can not be based on these other tumors.

There is a caveat- just finding drugable targets might not alter the outcome with DIPG.  So for this approach has not changed the prognosis in adult GBMs despite a huge amount of available tissue.  We are at the beginning.   We don't know yet.   There is hope and optimism that this is a start. 

References:

From boos to hope: Challenging the dogma about deadly brain stem gliomas

http://childrenshospitalblog.org/from-boos-to-hope-challenging-the-dogma-about-deadly-brain-stem-gliomas 

Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma
http://www.ncbi.nlm.nih.gov/pubmed/22190243

Dana Farber DIPG Research Receives a Half Million Dollars

Mikey loved baseball and the New York Yankees, the Doobie Brothers and his dog named Cody.   On Mikey's 11th birthday, January 6, 2008, life as this family knew it ceased to exist.   They first heard the letters- DIPG.  After radiation and a radiosensitizer trial ( Motexafin Gadolinium), his tumor shrank about 85% by April; but byAugust, he started to have right sided numbness, problems walking and difficulty swallowing.     Mikey Czech died on September 7, 2008.

In Mikey's memory, the Stephen J Czech family founded the Mikey Czech foundation with a mission  to establish a leading neuro-oncology translational research laboratory, raise awareness of DIPG, fund research and cure pediatric brain tumors.

In their search to find research trying to cure DIPG, they found a physician, Mark Kieran MD, PhD, completely frustrated at the lack of prognostic change for DIPG in 30 years and a desire to try a new approach.   Biopsies were essentially stopped in the early 1990s before it was even possible to study tumor molecular biology and now seemed to be the right time to take advantage of all the knowledge gained in neurosurgical technique, cancer pharmacology and tumor molecular biology to try to make a difference for DIPG kids.

Dogma doesn't change easily.  For year, Dr Kieran challenged his colleagues on this front.   Little by little others came to the same perspective.  In December 2012, a multi-institutional clinical trial with molecularly determined treatment for the newly diagnosed child with DIPG commenced at Boston Children's.   Today, five other institutions (Lurie Children's in Chicago, Johns Hopkins,  Seattle Children's, Cook Children's in Texas and Washington University in St Louis) also have this trial open.
Watch Dr Kieran discuss a one minute presentation on DIPG research  (open in a different window)

This trial faced other difficulties as well- in particular, funding.   This trial is using already known drugs  so isn't a trial that would be funded by a pharmaceutical company.   It was up to private funding to make this happen.   Mikey Czech Foundation has been a big part of this- and with the donation of a half million dollars today continues to be a sustained supporter of Dana Farber's leading edge work.

One should note that the Boston researchers have not been sitting around waiting for the trial to start.   Biospies have been happening for years in France.  With the financial backing of these foundations,  the researchers in France and Boston collaborated to look at 20 newly diagnosed DIPG specimens- before they could be changed by radiation and chemotherapy.  Here is a link to the abstract published last year.

In this fight we will take Mikey's motto:

"Never, Never, Never Give Up!"

Note- I am aware of several organizations that have come together to fund this innovative research- The Zach Carson DIPG Fund, the Ellie Kavalieros DIPG Fund, The Prayers From Maria Foundation, Children's Hospital of Los Angeles Imaging Center, The Pediatric Brain TUmor Research and Clinical Fund at Dana-Farber Cancer Institute,Stop and Shop Pediatric Brain Tumor Research Fund and Hope for Caroline

References:
The Mikey Czech Foundaiton Contributes $500,000 to DIPG Research at Dana-Farber Cancer Institute-Harvard Medical School (2013)
http://finance.yahoo.com/news/mikey-czech-foundation-contributes-500-121400450.html

The Mikey Czech Foundation Funds New Hope for Cancer Research (2012)
http://thecristianriverafoundation.blogspot.com/2012/01/mikey-czech-foundation-funds-new-hope.html

Molecularly Determined Treatment of Diffuse Intrinsic Pontine Gliomas (DIPG)
http://clinicaltrials.gov/show/NCT01182350

Mikey Czech Foundation
http://www.mikeyczech.org/