Multi-targeted Acute Myeloid Leukemia Approach Shows Promise

A new biological drug with a cure rate of 50% for lab mice with acute leukemia has been developed by a research team at the Hebrew University of Jerusalem. Co-targeting the kinases CKIα and CDK7/9 with inhibitors deprived leukemia cells of important oncogenes and induced apoptosis.

Leukemia produces a variety (and a high quantity) of proteins that together provide leukemic cells with rapid growth and death protection from chemotherapy.

Acute myeloid leukemia is one of the most aggressive cancers. While other cancers have benefitted from new treatments, there has been no encouraging news for most leukemia patients for the past 40 years.

Until now.

Drug-resistant Leukemic Cells

To date, most of the biological cancer drugs used to treat leukemia target only individual leukemic cell proteins. However, during targeted therapy treatments, leukemic cells quickly activate their other proteins to block the drug.

The result is drug-resistant leukemic cells which quickly regrow and renew the disease.

However, the new drug developed by Professor Yinon Ben-Neriah and his research team at the Hebrew University of Jerusalem (HU)’s Faculty of Medicine functions like a cluster bomb. It attacks several leukemic proteins at once, making it difficult for the leukemia cells to activate other proteins that can evade the therapy.

Furthermore, this single molecule drug accomplishes the work of three or four separate drugs, reducing cancer patients need to be exposed to several therapies and to deal with their often unbearable side-effects.

Dramatic Overnight Change

Additionally promising, is the new drug’s ability to eradicate leukemia stem cells. This has long been the big challenge in cancer therapy and one of the main reasons that scientists have been unable to cure acute leukemia.

“We were thrilled to see such a dramatic change even after only a single dose of the new drug. Nearly all of the lab mice’s’ leukemia signs disappeared overnight,”

said professor Ben-Neriah.

BioTheryX recently bought the rights to this promising drug from HU’s technology transfer company Yissum. Together with Ben-Neriah’s research team, they are now applying for FDA approval for phase I clinical studies.

The research was supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Israel Science Foundation (ISF)-Centers of Excellence, the European Research Council, Israel Cancer Research Fund Professorship, and Memorial Sloan Kettering Cancer Center Support Grant.

Waleed Minzel, Avanthika Venkatachalam, Avner Fink, Eric Hung, Guy Brachya, Ido Burstain, Eli Pikarsky, Irit Snir-Alkalay, Yinon Ben-Neriah
Small Molecules Co-targeting CKIα and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models
Cell DOI:https://doi.org/10.1016/j.cell.2018.07.045

Image: University of Edinburgh. CC BY-NC.

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