Photo by Rhoda Baer
In an attempt to crowd-source cancer research, a pair of Canadian organizations made a small molecule they developed freely available to researchers.
The goal was to fast-track the testing of new treatment strategies and facilitate sharing of the results.
Researchers have already completed preclinical studies of this molecule, a WDR5 inhibitor called OICR-9429, showing that it is active against breast cancer and acute myeloid leukemia (AML).
The organizations that developed OICR-9429 are the Ontario Institute for Cancer Research (OICR) and the Structural Genomics Consortium (SGC).
“In the time that it would normally take to negotiate a legal agreement to provide OICR-9429 to other research teams, we have received results back from our collaborators showing that it can kill 2 different types of cancer cells,” said Cheryl Arrowsmith, PhD, of SGC Toronto in Ontario, Canada.
“Opening our chemistry capabilities to the world’s scientists allowed us to crowd-source and accelerate the research.”
A study published in Nature Chemical Biology suggested that WDR5 is a therapeutic target for a subtype of AML, and OICR-9429 could therefore be used to treat the disease.
The researchers noted that mutations in C/EBPα occur in about 9% of AML cases and lead to the expression of a 30-kDa dominant negative isoform (C/EBPα-p30).
Their experiments revealed that C/EBPα p30 preferentially interacts with WDR5. So it was no surprise that OICR-9429 inhibited proliferation and induced differentiation in p30-expressing AML cells.
In a study published in Nature, OICR-9429 inhibited cancer cell growth in a panel of breast cancer cell lines driven by mutated forms of p53.
Researchers said this work has implications beyond breast cancer because p53 is mutated in at least half of all cancers and is dysregulated in others.
“It is remarkable how quickly our research results were translated into discoveries by the groups around the world,” said Rima Al-awar, PhD, of OICR in Toronto.
“We are looking forward to seeing more research conducted with OICR-9429 and showing that this new approach to early stage drug discovery has significant advantages.”
The SGC and OICR teams said they are continuing their collaboration to identify additional molecules to advance cancer drug discovery.
