Nav: Home

Despite failures, chemo still promising against dangerous childhood brain cancer, DIPG

March 25, 2020

The pediatric brain cancer known as diffuse intrinsic pontine glioma (DIPG) is almost uniformly fatal. In part, this is due to where and how it grows, forming as a diffuse net of cells in a part of the brainstem called the pons, which controls essential functions like breathing and swallowing. Another factor that makes DIPG especially dangerous is a lack of treatments - currently, there are no targeted therapies or immunotherapies proven effective to treat the condition, and the many chemotherapy clinical trials seeking to treat DIPG have been uniformly unsuccessful.

In fact, chemotherapy has been so unsuccessful against DIPG that researchers have questioned whether chemotherapy drugs are even able to reach the cancer. There is reason to believe they might not: Many drugs are unable to cross the blood-brain barrier that encapsulates the brain and central nervous system, and the pons is especially hard to reach. Now a study by University of Colorado Cancer Center researchers working at Children's Hospital Colorado and published in the journal Neuro-Oncology Advances offers insight into this question.

"The results were surprising and encouraging," says Adam Green, MD, CU Cancer Center investigator and pediatric brain cancer specialist at Children's Hospital Colorado. "The bottom line is that it looks like the medicine does reach DIPG tissue in good quantities that have the potential to be effective against the tumor."

In other words, the reason chemotherapy has been ineffective against DIPG is most likely the fact that we haven't found the right chemotherapy yet.

In the clinical trial, done in collaboration with Michael Wempe, PhD, director of the Medical Chemistry Core Facility at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, investigators gave one dose of the chemotherapy drug gemcitabine to newly diagnosed DIPG patients and then measured how much of this chemotherapy was present in patients' tumor tissue on their biopsy performed immediately afterward. The group also performed parallel studies in mouse models of human DIPG. The results in humans and mice were similar, independent of exactly where the tumor grew in the brain, and held across a few known tumor subtypes.

"We don't expect the one dose of chemo to be effective against the tumor, and so we were really asking families to take a leap of faith with us - to trust that it would be safe and that it would help answer an important question, both for their child and for future patients. To be the first family and patient was a really brave decision on their part," Green says.

"This research makes us very happy," says the father of the first child enrolled. "The fact that our daughter contributed makes us proud. Also, the experiment was so elegant in its design. I remember thinking how propitious it was to give a single dose of gemcitabine immediately before the biopsy she already needed to have. What a perfect way to test something that desperately needed testing but was otherwise untested and untestable!"

Importantly, the Children's Hospital Colorado team is a leading center for the treatment of pediatric brain cancer and has helped pioneer tumor biopsy as a standard part of DIPG treatment.

"We wouldn't biopsy a patient's brain just to look for chemotherapy. But because this is part of our standard procedure for diagnosis and treatment, we were able to also look in biopsy tissue for the accumulation of chemotherapy. It made us uniquely positioned to do this trial," Green says.

Green sees the state of DIPG as similar to the treatment of pediatric leukemia in the 1950s or pediatric neuroblastoma in the 1990s, both of which were incurable at the time, but for which new treatments have dramatically improved outcomes.

"These diseases required combination treatment approaches, and that's what we're aiming for," Green says.

The current finding, while preliminary, also has the potential to influence the focus and design of DIPG clinical trials. For example, another treatment strategy has been to explore the direct delivery of chemotherapy drugs to tumor tissue in ways that bypass the blood-brain barrier. The current study implies that in addition to innovative drug-delivery strategies, the field can continue to prioritize the search for new, better chemotherapy drugs to be delivered via the standard method of infusion.

"It's encouraging," Green says. "This shows that systemic chemotherapy could be part of the answer in treating these tumors. We just have to apply all we're learning about the biology of the tumors to find the right medicines. It gives us a lot of hope that if we find the right medicines, we'll be able to treat this tumor effectively."

University of Colorado Anschutz Medical Campus

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

There's so much we've yet to explore–from outer space to the deep ocean to our own brains. This hour, Manoush goes on a journey through those uncharted places, led by TED Science Curator David Biello.
Now Playing: Science for the People

#555 Coronavirus
It's everywhere, and it felt disingenuous for us here at Science for the People to avoid it, so here is our episode on Coronavirus. It's ok to give this one a skip if this isn't what you want to listen to right now. Check out the links below for other great podcasts mentioned in the intro. Host Rachelle Saunders gets us up to date on what the Coronavirus is, how it spreads, and what we know and don't know with Dr Jason Kindrachuk, Assistant Professor in the Department of Medical Microbiology and infectious diseases at the University of Manitoba. And...
Now Playing: Radiolab

Dispatch 1: Numbers
In a recent Radiolab group huddle, with coronavirus unraveling around us, the team found themselves grappling with all the numbers connected to COVID-19. Our new found 6 foot bubbles of personal space. Three percent mortality rate (or 1, or 2, or 4). 7,000 cases (now, much much more). So in the wake of that meeting, we reflect on the onslaught of numbers - what they reveal, and what they hide.  Support Radiolab today at