Novel Treatment Causes Cancer to Self-Destruct Without Affecting Healthy Cells

Source: Albert Einstein College of Medicine

Summary: Researchers have discovered a compound for the first time that makes cancer cells commit suicide without affecting the healthy cells.

Acute Myeloid Leukemia – AML (a type of blood cancer) accounts for 33% of all new leukemia cases and is responsible for the death of 10,000 Americans each year. The survival rates of AML patients have remained about 30% for decades, therefore novel treatments are needed to cure this condition. Researchers at Albert Einstein College of Medicine have discovered a compound that fights with cancerous cells by initiating the process called apoptosis (is a process of programmed cell death). Generally, apoptosis is initiated when the executioner protein – BAX is activated by the pro-apoptotic proteins but the cancerous cells for their survival produce large amounts anti-apoptotic proteins which in turn suppress the BAX and pro-apoptotic proteins. The new treatment approach was directed against AML cell and the entire approach is described in the journal Cancer Cell.

Apoptosis in cancer cells triggered by BAX protein

BAX protein (purple); BTSA1 (orange); active site of BAX (green); changing the shape of the BAX molecule at several points (shown in yellow, magenta and cyan); Credit: Albert Einstein College of Medicine

The discovered novel compound is termed as BTSA 1 (BAX Trigger Site Activator 1). BTSA 1 binds with the BAX’s activation site with high affinity and revives the suppressed BAX molecules in the cancerous cells. BAX, once activated can home in on mitochondria and puncture their outer membranes, triggering apoptosis in cancer cells and leaving healthy cells untouched. The whole treatment was examined in mice, by grafting human AML cells in to mice, researchers generated animal models of AML. 43% of the BTSA 1 treated AML mice survived even after 60 days with no signs of AML. The most important thing is, the mice treated with BTSA 1 showed no evidence of toxicity. The researchers want to further test BTSA 1 on animal models of other types of cancer.

Evripidis Gavathiotis, senior author of the study said, “We’re hopeful that the targeted compounds we’re developing will prove more effective than current anti-cancer therapies by directly causing cancer cells to self-destruct, Ideally, our compounds would be combined with other treatments to kill cancer cells faster and more efficiently—and with fewer adverse effects, which are an all-too-common problem with standard chemotherapies.”

More Information: Evripidis Gavathiotis et al, “Direct activation of BAX by BTSA1 overcomes apoptosis resistance in acute myeloid leukemia,” Cancer Cell (2017). DOI: 10.1016/j.ccell.2017.09.001

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