New Therapy Overcomes Drug-Resistant Leukemia

New Therapy Overcomes Drug-Resistant Leukemia

Researchers at The Institute of Cancer Research (ICR) in London made a new discovery that may represent a new treatment for patients with acute myeloid leukemia. Researchers discovered a new drug that can block tumor proliferation and prevent from resistance development of cancer cells.

FLT3 gene  mutation is encountered in acute leukemia with poor prognosis. The treatment of this sever forms is often ineffective because cancer cells develop resistance. Normally, FTL3 gene is involved in cell proliferation, but in patients with leukemia, FTL3 mutations cause a chaotic and uncontrolled replication of malignant cells. While drugs which are blocking the protein produced by FTL3 gene are available, cancerous cells become resistant to this drugs, making the treatment ineffective.

In order to prevent this events, scientists developed a “double hit drug”, which is blocking, on the one hand, the product of FTL3 gene and on the other hand is targeting another key protein called Aurora kinase. Aurora kinase present elevated levels in many cancer types and it was observed that is causing errors during cell division. Study of The Institute of Cancer Research (ICR) in London, funded by Cancer Research UK and Breakthrough Breast Cancer, had positive results: half of the mice treated with this drug had complete remission of the disease. Therefore, they are thinking about  introducing  this new drug in clinical trials to prove efficacy in humans.

Acute Myeloid Leukemia

Acute myeloid leukemia represents 80% acute leukemias in adults. Acute myeloid leukemia is characterized by uncontrolled proliferation of myeloid cells, bone marrow being occupied by cancer cells that interfere with normal production of blood cells. This events explain the signs that occur in people with acute myeloid leukemia: anemia (low red blood cells count), neutropenia (low neutrophil counts) and thrombocytopenia (low platelet count). Symptoms occurring in patients with acute myeloid leukemia are asthenia, fatigue, bruising (even after minor lesions), dyspnea, infections.

FTL3 gene encodes a protein called FTL3 (Fms-like tyrosine kinase 3) with a receptor role that is  found on the surface of hematopoietic progenitor cells. It also called CD135 and plays an important role in oncogenesis, because mutations of CD135 are promoting malignant cell development (is a protooncogene). The most common mutations of FTL3  associated with acute myeloid leukemia are represented by  internal tandem duplications.

So far, many treatments schemes that include FTL3 inhibitors, such as sunitinib, sorafenib, midostaurin, have been tried, but the results were not promising. Lead author Dr. Spiros Linardopoulos, leader of the Cancer Drug Target Discovery Team at The Institute of Cancer Research, said that there was a great interest these FTL3 inhibitors, but their effectiveness was limited because cancer cells have developed resistance due to mutations. He also added that the new drug may be a solution not only for patients aged over 60 years who can not manage chemotherapy, but also for those with relapses.