Investigators at St. Jude Children’s Research Hospital have discovered that the ABCC4 transporter is critical to the SHH signaling pathway in the brain tumor medulloblastoma. This work provides a rational for development of small molecule inhibitors that target ABCC4.

What are medulloblastomas?

These are the most common type of primary brain cancer in children. It originates in the part of the brain that that is towards the back and the bottom, on the floor of the skull, in the cerebellum. This form of cancer is invasive, rapidly growing tumors that spread through the cerebrospinal fluid and frequently metastasize to different locations along the surface of the brain and spinal cord. 

Study Context

These findings were recently published in Cancer Research and pointed that medulloblastoma is the most common malignant pediatric brain tumor. St. Jude Children’s Research Hospital reported in their news release four genomic subgroups of the disease including: WNT, SHH, Group 3 and Group 4. The SHH subgroup accounts for about a quarter of all pediatric medulloblastoma cases. For this group, the five-year survival rate for SHH medulloblastoma is about 75%. The researchers published their results in Cancer Research in the Jan. 16, 2020 edition.

What are transporters?

Proteins found on the cell membrane.  They help substances enter and exit cells.

What did the researchers at St. Jude find?

They found that the ABCC4 transporter is highly expressed in SHH medulloblastoma.

What was the breakthrough for the St. Jude Department of Pharmaceutical Sciences researchers?

John Schuetz, PhD  reported that they have been investigating the transporter (ABCC4) for years and sought to comprehend “how it interacts with critical pathways that drive tumor growth, like SHH.” Hence the study team analyzing the interconnected dynamics of ABCC4 and the SHH pathway they were able to develop a novel strategy for new treatment approaches.

What did the St. Jude investigators design?

The researchers build a medulloblastoma “interactome” to assess which proteins interact with and are essential to the SHH pathway. The findings revealed that ABCC4 is highly expressed in the SHH subgroup and is required for optimal activation of the pathway.

What did the St. Jude investigators find?

They found that increased expression of ABCC4 correlates with poor overall survival in SHH medulloblastoma. Targeting ABCC4 using genomic methods reduced the size of medulloblastoma tumors and extended lifespan of mouse models.

Lead Research/Investigators

John Schuetz, PhD  

Juwina Wijaya, PhD

Source: St. Jude Children’s Research Hospital

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