The SCC project has entered the next phase of the research and new workunits have been prepared for the BOINC restart.
Background
While the proteins and other molecules that play key roles in childhood cancers have been identified, finding chemical compound (drug) candidates that can target these molecules and modify their function is a lengthy process. Using the computing power of WCG, the Smash Childhood Cancer team has been able to search millions of drug candidates for possible clinical application.
The project has been running intermittently, identifying possible drug candidates and then testing them in the lab. As of December 2020, 48,000 years of calculations have been donated to the SCC team by WCG volunteers. Since then, the team has been busy validating the results they received (see recent updates).
March 2023 update
We are excited to share an update from the Smash Childhood Cancer team about the start of the new phase in their quest for curing cancer. The new target protein is MyoD1 (Myogenic Differentiation 1 protein) and one of its mutations, L122R. MyoD1 is a transcription factor that activates muscle-specific genes, and is involved in the switch between cell growth and cell differentiation. The loss of control over this switch can cause the formation of rhabdomyosarcomas1.
L122R is a mutation frequently found in rhabdomyosarcoma, and it is linked to a worse prognosis2. Considering the crystal structure deposited in Protein Data Bank, the goal is to find compounds that act on the mutant-type but not on the wild-type.
Crystal structure of MyoD bHLH domain-DNA complex: perspectives on DNA recognition and implications for transcriptional activation3.
New SCC work units have been prepared to help with the search, and volunteers who follow this project will be able to download them once we restart BOINC after the storage failure.
If you have any comments or questions, please leave them in this thread for us to answer. Thank you for your support, patience and understanding.
WCG team
Sources:
- Sebire NJ, Malone M. Myogenin and MyoD1 expression in paediatric rhabdomyosarcomas. Journal of Clinical Pathology 2003;56:412-416.
- A MYOD1 Mutation Cooperates with PI3K Pathway Activation in ERMS. Cancer Discov 1 July 2014; 4 (7): OF19. https://doi.org/10.1158/2159-8290.CD-RW2014-109.
- Crystal structure of MyoD bHLH domain-DNA complex: perspectives on DNA recognition and implications for transcriptional activation. Ma, P.C., Rould, M.A., Weintraub, H., Pabo, C.O. Cell 77: 451-459. PubMed: 8181063. PDB DOI: https://doi.org/10.1016/0092-8674(94)90159-7