Smash Childhood Cancer (SCC) team provided an exciting update on the validation results for the three projects.
As scientific discoveries on the WCG platform take considerable time to be analyzed and validated, it is with great enthusiasm we share with you a recent update from Smash Childhood Cancer team.
Making Chemotherapy Work Better: PAX-FOXO1 inhibitors for childhood muscle cancer
In work supported by the Megan's Mission Foundation, the Children's Cancer Therapy Development Institute (cc-TDI.org; under leadership of Dr. C. Keller) has collaborated with Dr. Tyuji Hoshino at Chiba University and the World Community Grid (WCG) to develop the unlikely drug: an inhibitor of a 'transcription factor'. In the childhood muscle cancer rhabdomyosarcoma, the two normal transcription factors PAX3 and FOXO1 'break' and then fuse to one another. The resulting PAX-FOXO1 transcription factor drives a program of other genes to go on that lead to chemotherapy resistance, relapse and sometimes demise. Through the WCG, 8 million compounds were screened and a mere 24 compounds were identified. Thus far, 5 have been validated to stop the action of the PAX-FOXO1 transcription factor. The cc-TDI project lead is Kiyo Nagamori.
Stopping Metastasis of Childhood Sarcomas
In work supported by the Pheonix Spangler Foundation, the Children's Cancer Therapy Development Institute (cc-TDI.org) has collaborated with Dr. Tyuji Hoshino at Chiba University and the World Community Grid (WCG) to develop a small molecule inhibitor of the Osteopontin protein. Osteopontin is a protein made by cancer cells as a way to invite blood vessels to grow nearer. These vessels are then a pathway to spread throughout the body. In work evaluating computationally-modeling chemicals and experimentally identified compounds from collaborator Aykut Uren at Georgetown University, we have identified compounds that bind Osteopontin. The next step is to determine if these compounds stop the blood vessel formation and metastasis that occur as a result of Osteopontin. Genetically-engineered mice with normal levels or absence of Osteopontin make this work possible. The cc-TDI project lead is Shefali Chauhan.
Stopping the Driver of TrkB Neuroblastoma
In studies honoring Alyssa, the Children's Cancer Therapy Development Institute (cc-TDI.org) has collaborated with Dr. Tyuji Hoshino and Dr. Akira Nakagawara at Chiba University and the World Community Grid (WCG) to develop next-generation, selective inhibitor of the TrkB protein. TrkB drives the growth and progression of childhood nerve cell cancer, neuroblastoma. TrkB is the sister protein to TrkA, which has become of great pharmaceutical interest in sarcomas and lung cancers. The TrkB inhibitors developed by evolving chemicals derived from computational modeling have increased solubility but retain activity against TrkB. The cc-TDI project lead is Xiaolei Lian.
Thank you Dr. Keller and the rest of the SCC team for your incredible work. We look forward to hearing about further success of these treatments, and to run new predictions on the WCG for the new targets.
WCG team at Krembil Research Institute