Dr. Vivekanand Yadav is hopeful it can.
by Jen DeGregorio, Director of Communications
For families faced with the devastation of a DIPG diagnosis, time is priceless. It was for that very reason that Tammi and Jason Carr decided to donate tissue from their son Chad’s tumor to research when he passed away from the disease in 2015.
For decades, little was known about DIPG, the most deadly and aggressive form of brain cancer. Now, sequencing from Chad’s tumor continues to offer rich insight into how DIPG progresses.
In a recent interview with Dr. Vivekanand Yadav, who was awarded a ChadTough Defeat DIPG New Investigator Grant in 2021, we learned more about his findings while studying the effects of cannabidiol (CBD) on DIPG tumors and how Chad’s tissue sample has helped him further his work.
CTDDF: Can you tell me a bit about yourself and how you decided to work in the world of brain cancer research?
Dr. Vivekanand Yadav: I am an Assistant Professor in the Department of Pediatrics at Children’s Mercy Research Institute (CMRI) in Kansas, pursuing DIPG research with the goal of providing better treatment options for kids diagnosed with devastating DIPG cancer. During my postdoctoral neuro-oncology research training at the University of Michigan, I gathered extensive experience in adult and pediatric high-grade gliomas and developed novel epigenetic mouse models of DIPG. I am equipped with an excellent team of researchers, collaborators, and funding support from CMRI and the ChadTough Defeat DIPG Foundation to continue my DIPG research.
I’ve always been passionate about brain cancer research. As brain tumors remain among the deadliest of all cancer forms, it is one of the most common and leading causes of cancer-related death in children. Learning about the challenges related to the brain cancer field and interacting with so many knowledgeable and compassionate professionals inspired me to work on brain cancer research with the hope of identifying new therapeutic targets and providing a better treatment outcome in the future.
CTDDF: In following your research, we learned that when a normal brain stem develops, a gene called ID1 is expressed to help aid in growth. This gene usually shuts off after birth, however you’ve found that ID1 is also very highly expressed in DIPG tumors. The presence of this gene promotes tumor growth and drives DIPG cells to travel quickly and invade normal tissue. Can you tell me more about this and how this discovery could potentially help in future therapies?
Dr. Vivekanand Yadav: In this study, we indeed found that the ID1 gene is highly expressed in DIPG tumors and drives the DIPG cells to migrate (travel) and invade normal tissue, perhaps at least partially explaining why the DIPG tumor is so aggressive in nature. We also found that genetic and pharmacologic (CBD) suppression of ID1 decreases DIPG tumor cell invasion/migration and tumor growth.
The poor prognosis of DIPG is partly attributed to the tumor’s highly invasive growth into normal brain tissue. In this report, we show that inhibition of ID1 with CBD slows tumor invasion/growth, which provides a small but significant bump in survival in mice with DIPG tumors. It’s a strong case to bring CBD into a DIPG trial, though alongside another drug as monotherapy is unlikely to bring enough efficacy; this will allow the field of DIPG research to finally learn if and how we should use CBD in patients diagnosed with DIPG. By the completion of this project, we hope to address a key knowledge gap of how H3K27M rewires ID1 expression to drive DIPG tumor growth and provide critical mechanistic insight into a therapy (CBD) that is highly popular among DIPG patients but remains understudied.
CCDDF: We were pleased to help support your work with a 2021 New Investigator grant. What do you feel is the importance of private funding in moving the field of DIPG forward?
Dr. Vivekanand Yadav: Private funding, including the DIPG grants funded by ChadTough Defeat DIPG, plays a crucial role in developing new innovative research ideas. The recently announced graduate and postgraduate research fellowships will encourage junior-level researchers to pursue their careers in DIPG research. The private funding would help uncover new targets that may provide a new therapeutic approach and extend the lives of children with DIPG.
CCDDF: Can you comment on the current state of DIPG treatment in general? For example, how have things changed since Chad Carr was diagnosed in 2014?
Dr. Vivekanand Yadav: Since Chad Carr was diagnosed in 2014, many DIPG researchers have made tremendous efforts to identify new promising therapy using patient-derived DIPG cells, including sequencing from Chad’s tumor. Genomic approaches have been utilized to develop patient-specific therapeutic strategies based on the specific oncogene activation. Several recent clinical trials based on immunotherapies and chemotherapies have increased our understanding of DIPG biology. We hope to see some effective therapy soon.
ChadTough Defeat DIPG Foundation is proud to be supporting this cutting-edge work, and we look forward to following the progress in Dr. Yadav’s research. To learn more about his study, visit https://academic.oup.com/neuro-oncology/advance-article/doi/10.1093/neuonc/noac141/6590903.