The team is progressing in its effort to validate compounds inhibiting molecules with important roles in most frequent childhood cancers
Background
The Smash Childhood Cancer research team has identified proteins and other molecules that play key roles in the most common childhood cancers. The challenge is now to find drug candidates that specifically target these key molecules and therefore control the cancer cells.
Data analysis updates
Since last year, the SCC team has been analyzing data computed on the WCG, and synthesizing and testing prioritized compounds.
Below are some of the most promising proteins, which are involved the development of at least one type of childhood cancer.
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Germ Cell Tumor - PRDM14 project
Germ cell tumors are a unique group of tumors that occur in the gonads and extragonadal locations. One type of extragonadal germ cell tumor occurs in the brain. The current treatment for the brain germ cell tumors can cause lots of side effects, therefore, we wanted to identify a new therapy for this group of patients. In this project, we are targeting a protein PRDM14 and its co-partner CBFA2T2.
Normally, PRDM14 is only present in the early fetus and requires CBFA2T2 to help carry its function. However, some tumors, such as germ cell tumors, express PRDM14 and CBFA2T2.
We have been doing in vitro testing of the available compounds that were predicted to disrupt PRDM14-CBFA2T2 interaction. We have screened 16 compounds so far for their ability to kill germ cell tumor cell lines. Two of the compounds showed promising results, and are being further tested.
EWSR1-type Tumor Drug Development
These types of tumours present a very specific mutation that fuses EWSR1 with a transcription factor, making them more active than what they should be.
The Keller lab at cc-TDI.org has active inhibitors, and now are testing whether they have any undesired, off target effects.
TrkB Inhibitors for Childhood Neuroblastoma
Neuroblastomas start in some immature nerve cells, and most frequently affects infants and younger children.
One of Dr. Hoshino's drug precursors has specific activity in tumor cell lines (it does not target non TrkB expressing cells), when tested at the cc-TDI.org lab. Validation studies of these very promising results are ongoing.
PAX-FOXO1 inhibitors for Childhood Rhabdomyosarcoma
The Keller lab at cc-TDI.org is perfectioning a new validation
assay for one promising inhibitor compound.
Dr. Chen is also finalizing the Entinostat clinical trial design at Hong Kong University.
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Current status of work units
Paused
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