Oregon Health & Science University Cancer Institute researchers have found a new, experimental drug candidate it to be effective against a highly resistant mutation in chronic myeloid leukemia (CML).
This drug candidate could build on the legacy of Gleevec, which has been the gold standard for treating this leukemia and was developed by Brian Druker, M.D., director of the OHSU Cancer Institute. Despite Gleevec's success, some CML patients develop resistance to Gleevec, often due to mutations that interfere with drug binding. The second-generation drugs Sprycel and Tasigna have been developed as largely successful treatments for Gleevec-resistant patients. However, one mutation, termed T315I, is completely resistant to all three clinical CML drugs and is a frequent cause of relapse.
Now, however, a new drug candidate, SGX393, has been found to inhibit most resistant mutations, including T315I, both in mouse models and in patient cells in laboratory studies. SGX393 was identified by SGX Pharmaceuticals Inc., a biotechnology company focusing on cancer therapeutics.
The OHSU Cancer Institute researchers took this a step further.
“Because none of the drugs controlled all of the known mutations, we extended our study to look at using combinations of the drugs,” said Christopher Eide, research technician, hematology/medical oncology, OHSU School of Medicine.
“Remarkably, we found that the combination of SGX393 with either Sprycel or Tasigna completely suppressed resistant growth. Our findings raise the exciting possibility that inhibitor ‘cocktails' may be sufficient to completely pre-empt drug resistance in CML,” Eide said.
He is a co-author with OHSU Cancer Institute research scientist Thomas O'Hare, Ph.D., research specialist, hematology/medical oncology, OHSU School of Medicine.