Taking his "repurposing" system out for a run, Dakshanamurthy and his team screened almost 4,000 FDA approved drugs across more than 2,000 protein structures. He came across five big, promising "hits," one of which he brought to Byers.
Dakshanamurthy had found that the arthritis drug Celebrex fits neatly into the cadherin-11 protein structure.
"This was amazing," Byers says.
So Byers, Brenner, and Dakshanamurthy had each, independently, contributed to the new understanding that Celebrex and sd133 and Brenner's antibody might effectively stop growth of untreatable tumors as well as rheumatoid arthritis.
That put Byers in the right position to be able to answer PQ no. 5 can any of their candidate agents stop both cancer and arthritis, and how does it work?
Folded into Byers' PQ collaboration is Columbia University structural biologist Lawrence Shapiro, Ph.D., who was first to determine the crystal structure of cadherin-11. Shapiro plans to build the structure of cadherin-11 bound to Celebrex.
"We need to figure out how cadherin-11 actually transmits a signal and what that signal is that allows cancer cells to grow and causes the symptoms of rheumatoid arthritis," Byers says.
He can't help but be optimistic about the potential answer that his PQ team will turn in to the NCI findings that may translate quickly into advancements in the treatment of some very difficult diseases. Says Byers, "The prospect of using a drug developed for arthritis in cancer is very powerful."
|Contact: Karen Mallet|
Georgetown University Medical Center