New insight into how tumor cells can become resistant to anti-cancer therapy

A new study by researchers at Memorial Sloan-Kettering Cancer Center and The Johns Hopkins University provides new insight into how tumor cells can become resistant to anti-cancer therapy.

The scientists observed that a protein called P-glycoprotein (P-gp), which causes resistance to chemotherapy in many tumor types, is able to physically “jump” or transfer between tumor cells and retain its functional properties, protecting otherwise sensitive cells from the effects of anti-cancer treatment in vivo and in vitro. According to the authors, the research is the first to demonstrate that a protein transferred between cells retains its function long enough to allow the recipient cells to survive potentially toxic drug concentrations and ultimately develop intrinsic resistance.

In other words, cells that would normally be sensitive to treatment can develop resistance to it by receiving P-glycoprotein from other cells, making chemotherapy much less efficient. Uncovering the mechanism of this unusual “jumping” of the protein between the cells can potentially improve treatment success.

The authors conclude that their findings offer a new way in which to look at how cells behave in a community of cells within a tumor mass. The results have important implications for genomic analyses within tumor samples because resistance to cancer therapy can be achieved by protein transfer alone.

The new research will be published the week of January 17, 2005 in the online Early Edition of the Proceedings of the National Academy of Sciences (PNAS).

The senior corresponding author of the paper is Steven Larson, MD, Chief of the Nuclear Medicine Service at Memorial Sloan-Kettering Cancer Center.

The lead author is Andre Levchenko, formerly of Memorial Sloan-Kettering Cancer Center and currently assistant professor in the Department of Biomedical Engineering at The Johns Hopkins University.

The work was supported by the Department of Energy, The Whitaker Foundation, and Memorial Sloan-Kettering Cancer Center.