Leukemia Drug May Override All Gleevec Resistance -- MEDICA - World Forum for Medicine

Leukemia Drug May Override All Gleevec Resistance

Scientists are getting a grip on
mutant Gleevec-resistant CML

According to lead researcher Prem Reddy, Ph.D., professor of biochemistry and Director of the Fels Institute for Cancer Research at Temple University School of Medicine, most patients with advanced CML typically develop resistance to Gleevec within a few years of starting the therapy.

Gleevec works by binding to the cancer protein BCR-ABL and completely blocking its activity, stopping cancer growth. When Gleevec came to market about four years ago, it was widely hailed as a miracle drug.

"Gleevec has been a remarkable success for the treatment of CML. However, a significant number of patients eventually develop resistance to it because their cancer cells are able to mutate and adapt,” said Reddy.

Recently, two drugs were found to be effective in circumventing some but not all forms of Gleevec resistance. They failed to block the activity of a mutant BCR-ABL, called T315I, which is one of the more predominant mutations seen in Gleevec-resistant patients.

Reddy and his research team sought instead to develop a drug that would circumvent all of the mutations and therefore all forms of resistance. They focused on other possible avenues to inhibit the actions of BCR-ABL. To do so, they targeted parts of the BCR-ABL protein that didn't appear to be mutating and adapting to Gleevec.

"We developed ON012380, a compound that specifically inhibits BCR-ABL by blocking a different site in the protein, which is essential for its activity. As a result, ON012380 was found to induce cell death of all of the known Gleevec-resistant mutants and cause regression of leukemias in human tumour cells and in animal models,” explains Reddy, who is currently seeking FDA approval to proceed with clinical trials.

"Our drug works just like Gleevec but by blocking another part of the BCR-ABL protein. It can be combined with Gleevec to create synergy and when patients become resistant to Gleevec, our drug kills 100 percent of the cancer cells,” said Reddy.

MEDICA.de; Source: Temple University