Hi Frank, you may have read this already…sounds exciting!
Histone Deacetylase Anti-Cancer Effect Tied to TRAIL
January 3, 2005 (Reuters) –
NEW YORK – Mechanisms by which histone deacetylase inhibitors (HDACIs) act selectively to eliminate acute myeloid leukemia (AML) cells appear to involve induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), also known as Apo2 ligand, European researchers report in an advance online edition of Nature Medicine published Dec. 26.
As senior investigator Dr. Lucia Altucci told Reuters Health, “several of these HDACIs are already enrolled in clinical trials at phases I and II, targeting hematological malignancies and solid cancers, and promising results are being obtained.”
HDACIs, such as valproic acid and MS275, either alone or in combination with other compounds, have been shown to induce cell cycle arrest, differentiation and apoptosis in cancer cells, but not in normal cells, Dr. Altucci of the University of Naples and colleagues note.
To help elucidate what factors might be at work, the researchers conducted a number of studies involving the action of MS275 and other HDACIs on human lymphoma U937 cells, SCID mice with xenografts and blast cells from AML patients.
Among findings was that “MS275 induced apoptosis in the overwhelming majority of AML blasts, correlating with TRAIL induction.” The researchers also found that the survival of normal cells is not notably affected by MS275 or by TRAIL.
They conclude that the action of TRAIL underlies the selective effect of HDACIs on cancer cells.
“The importance of these findings,” added Dr. Altucci, “is that for the first time, a cancer drug attacks selectively the tumor and has no harmful effect on normal cells.”
Nat Med 2004.
Copyright 2005 Reuters Limited.
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