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For most people, cancer is a very scary word. And acute myeloid leukemia (AML) – one of the most relentless types of malignancies – is among the most frightening of all. Earlier this year. some new therapies emerged, yet they are given mainly in combination with chemotherapy developed 50 to 60 years ago and with no promise of a cure.

While other cancers have benefitted from new treatments, there has been no encouraging news for most leukemia patients for the past four decades – until now.

Hebrew University of Jerusalem researchers have developed a new biological drug with a cure rate of 50% in laboratory mice that have AML. The scientific journal Cell has just published the discovery of Dr. Yinon Ben-Neriah and his research team at the university’s Faculty of Medicine.

“We were very excited to notice a dramatic effect made with a single-dose treatment of the new drug. Nearly all the leukemia signs disappeared from a sick mouse overnight,” said Waleed Minzel, the doctoral student who led the rodent studies.

In this type of cancer, the bone marrow makes abnormal myeloblasts (a type of white blood cell), red blood cells or platelets. Leukemia produces a variety and a large number of proteins that, together, provide leukemic cells with rapid growth and death protection from chemotherapy.

Smoking, previous chemotherapy treatment and exposure to radiation may increase the risk of adult AML. Signs and symptoms of adult AML include fever, shortness of breath, easy bruising or bleeding, weight loss or loss of appetite, tiredness and easy bruising or bleeding. This type of cancer usually gets worse quickly if not treated.

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Scientists have learned that leukemia cells produce proteins that are barely made in normal blood cells, as well as mutated abnormal proteins (oncoproteins). Biological cancer drugs developed so far mostly attack a single leukemic protein; the leukemic cells quickly find a way to avoid the drug effect through alternative proteins. This results in survival of enough drug-resistant leukemic cells which regrow quickly and renew the disease.

Unlike most modern cancer drugs, the newly developed drug by Ben-Neriah and colleagues works like a cluster bomb that simultaneously attacks many leukemic proteins and thus makes it difficult for the leukemia to evade the therapy. This multi-targeted attack thus accomplishes with a single molecule what is ideally achieved with three or four separate drugs, without paying the unbearable toll that is often encountered with combination therapy. Another important advantage of the new drug is its capacity to eradicate leukemia stem cells, which is a big challenge in cancer therapy and one of the main reasons for failing to cure cancer.

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 Ben-Neriah and his team 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. Further, 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.

The new drug also has the ability to eradicate leukemia stem cells that have long been the big challenge in cancer therapy and one of the main BioTheryX, a US-based company, 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. BioTheryX is preparing now with the research team to apply for Food and Drug Administration approval for phase I clinical studies in the US.

The drug research was funded by the Dr. Miriam and Sheldon Adelson Medical Research Foundation, the Horizon 2020 – European Commission, the Israel Science Foundation’s Centers of Excellence and the Israel Cancer Research Fund.

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