Cell Therapeutics, Inc. (CTI) has announced the presentation of findings from a preclinical study of PIXUVRI® (pixantrone) that suggest its mechanism of inducing tumor cell death is novel and distinct from that of anthracyclines such as doxorubicin.
PIXUVRI is a first-in-class aza-anthracenedione with unique structural and physiochemical properties that is currently approved in the European Union for use as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell non-Hodgkin lymphoma.
The study results were presented by Neil Beeharry, Ph.D., at the Fox Chase Cancer Center during a poster session at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics held October 19-23, 2013 in Boston, MA.
"The study results suggest that PIXUVRI is unique in its mechanism for inducing tumor cell death, thereby supporting the thesis that it is the first approved drug in a new class of anti-cancer agents. PIXUVRI's mechanism of action is differentiated from the cytotoxic action induced by anthracyclines and could be the basis for the efficacy and safety profile of the drug," stated Dr. Beeharry.
The study assessed the mechanism of tumor cell killing induced by PIXUVRI in a variety of cancer cell lines. Specifically, the study assessed the impact PIXUVRI had on cell proliferation and time to cell death, the cell cycle, DNA damage response and longer term effects on cell division.
Unlike anthracyclines - which kill both normal and cancer cells with short-term exposure - PIXUVRI had minimal short-term effects on cell survival, but probably through formation of stable DNA adducts, caused delayed but efficient tumor cell death. This effect was not dependent on the presence of the p53 gene, a gene associated with recognition of chromosomal damage and apoptosis.
Loss of p53 was only associated with a further delay in cell death with longer exposure to PIXUVRI. The authors concluded that PIXUVRI appears to be impairing chromosomal segregation during mitosis, thereby generating loss of genetic material in daughter cells, an abnormality, which is ultimately lethal, and that PIXUVRI would likely be effective in cells resistant to other cytotoxic agents such as doxorubicin. The authors are pursuing leads to further understand the exact mechanism of action.