FINDING A CURE FOR DIPG
– ONE CELL AT A TIME

Diffuse Intrinsic Pontine Gliomas (DIPGs) are the most lethal brain tumors afflicting children. Most succumb to their disease within a year of diagnosis. Pediatric patients are currently treated with radiation therapy and often chemotherapy; however, tumors exhibit rapid resistance to these therapies and commonly start to grow again within months of treatment completion. Understanding the biology of DIPG is critical in order to identify new effective treatments for this disease.

While considerable progress has been made in the identification of molecular subtypes of many cancers, the transfer of these findings into improved therapies for children with DIPG has not yet been realized. Genetic studies of DIPG have recently shed light on their mutations, but much remains to be learned about how this tumor starts growing and maintains itself. One key limitation to current analyses is that they are performed on bulk tumor pieces and do not inform at the single-cell level or on the functional states of individual cells.

Our hypothesis is that DIPG is a heterogeneous disease containing many diverse cell types. Only a small percentage of cells have the potential to cause the tumor to grow by aberrantly reactivating stem-cell genes that were turned off after normal brain development.

Our proposed research leverages single-cell RNA sequencing technologies and applies them directly to patient samples. These novel methods are revolutionizing our understanding of cancer, as they allow for the first time to look comprehensively (up to 10,000 active genes in any given single cell) at all cell types present in a tumor, including rare sub-populations. This will enable us to identify all cell types in patient-derived DIPG biopsies in an unbiased fashion, identify their genetic mutations, and characterize the programs that drive them at the single-cell level for the first time. Uncovering these aspects of DIPG tumor biology will effectively fill a very large gap of knowledge and allow the design of therapies aimed at targeting the entire spectrum of DIPG cancer cell subpopulations that exist in patients.

Diffuse Intrinsic Pontine Gliomas (DIPGs) are the most lethal brain tumor afflicting children. Most succumb to their disease within a year of diagnosis. Pediatric patients are currently treated with radiation therapy and often chemotherapy; however, tumors exhibit rapid resistance to these therapies and commonly start to grow again within months of treatment completion. Understanding the biology of DIPG is critical in order to identify new effective treatments for this disease.

While considerable progress has been made in the identification of molecular subtypes of many cancers, the transfer of these findings into improved therapies for children with DIPG have not yet been realized. Genetic studies of DIPG have recently shed light on their mutations, but much remains to be learned about how this tumor starts growing and maintains itself. One key limitation to current analyses is that they are performed on bulk tumor pieces and do not inform at the single-cell level or on the functional states of individual cells.

Our hypothesis is that DIPG is a heterogeneous disease containing many diverse cell types. Only a small percentage of cells have the potential to cause the tumor to grow by aberrantly reactivating stem-cell genes that were turned off after normal brain development.

Our proposed research leverages single-cell RNA sequencing technologies and applies them directly to patient samples. These novel methods are revolutionizing our understanding of cancer, as they allow for the first time to look comprehensively (up to 10,000 active genes in any given single cell) at all cell types present in a tumor, including rare sub-populations. This will enable us to identify all cell types in patient-derived DIPG biopsies in an unbiased fashion, identify their genetic mutations, and characterize the programs that drive them at the single-cell level for the first time. Uncovering these aspects of DIPG tumor biology will effectively fill a very large gap of knowledge and allow the design of therapies aimed at targeting the entire spectrum of DIPG cancer cell subpopulations that exist in patients.

Find out more and help us on www.fightDIPG.org