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Novel Strategy for Treating CML: Repurpose Existing Anticancer Agents

By: Kayci Reyer
Posted: Monday, January 27, 2020

According to research published in the Asian Pacific Journal of Cancer Prevention, some well-known medications may have the potential to be reformulated into treatments that target progressive or resistant disease in patients with chronic myeloid leukemia (CML). Among the top candidates selected for repurposing in this study were the chelating agent deferoxamine, the type II topoisomerase inhibitor mitoxantrone, and the chemoprotectant leucovorin.

“Our study not only extends our current knowledge about repurposing drugs for newer indications but also provides a route towards combinatorial therapy with standard drugs used for CML treatment,” concluded Thangarajan Rajkumar, MD, PhD, of the Cancer Institute in Chennai, India, and colleagues.

The study relied on in silico methods to identify existing medications that might be repurposed to block the binding of growth factor receptor–bound protein-2 (G4b-2) to the BCR protein, thereby inhibiting disease progression. First, a data set from Gene Expression Omnibus was obtained, including hematopoietic cells from nine patients with Philadelphia chromosome–positive CML both prior to and after imatinib treatment as well as bone marrow samples from nine disease-free participants. An association was identified between differentially expressed genes and “hematopoietic cell lineage, NK cell-mediated cytotoxicity, NF-κB and chemokine signaling, cytokine-cytokine receptor interaction, histidine metabolism, and transcriptional misregulation in cancer.”

Based on gene-expression profiling, a list of correlated existent medications was identified by the Connectivity Map medication database. A total of 32 potentially reformulable medications, including antibiotics, flavonoids, contrast agents, and antimicrobials, was identified. Of those agents, nadide, hesperidin, butirosin, ovoflavin, and nordihydroguaiaretic acid had the strongest interactions on the relevant area of the BCR protein.

Disclosure: For full disclosures of the study authors, visit journal.waocp.org.



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