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A prominent worry amongst physicians treating cancer is a development of resistance to the chemotherapeutic drug. While many avenues are being explored for reducing chemoresistance, there is a growing need to discover novel methods to enhance cellular sensitivity to the drug. A new study from University of Michigan Assistant Professor of Physics and Biophysics Sarah Veatch, in collaboration with colleagues in radiation oncology, has shown the possibility of changing the physical properties of the cell membrane to enhance or suppress the effectiveness of a commonly used chemotherapeutic drug, Cisplatin, in cancer cell lines. This study has been published in PloS ONE.
Assistant Professor Veatch and her collaborators in the Department of Radiation Oncology–consisting of Assistant Professor Dipankar Ray and Associate Professor Mukesh Nyati–discovered a novel correlation between the ability of the drug to disrupt the lateral organization of the plasma membrane and the degree to which a cell is resistant to Cisplatin. The drug reduced the heterogeneity of the plasma membrane of cells that were more likely to be killed by the drug, but the drug did not have this effect on resistant cells. Interestingly, even radiation treatment used commonly in cancer treatments reduced the membrane heterogeneity.
The researchers exploited this correlation to reduce the heterogeneity in resistant cell lines along with the cisplatin treatment. This combination increased the effectiveness of the treatment in cells with moderate drug resistance. The researchers also found that they could do the reverse: make a cell more resistant to the drug by making the plasma membrane more heterogeneous. Further, these combination treatments did not change the concentration of the drug inside the cell, but rather made the drug more or less potent.
The researchers believe this proof of concept can now be expanded to more relevant model systems. It is also possible that the effectiveness of drug usage can be predetermined using the membrane’s physical properties as a surrogate marker for resistance. The researchers also caution that for this to be used in patient care, more translational research involving these novel class of chemosensitizers need to be done.
This study was funded through the University of Michigan’s MCubed program. Housed in the University of Michigan's Office for Research (UMOR), MCubed is part of the Third Century Initiative, established by the provost and president in anticipation of the university's bicentennial celebration in 2017. Building upon U-M's excellence and spirit of cooperation across the disciplines, MCubed makes great ideas go!
Krishnan Raghunathan, Aarif Ahsan, Dipankar Ray, Mukesh K. Nyati , Sarah L. Veatch, ‘Membrane Transition Temperature Determines Cisplatin Response’ PLoS ONE 10(10):e0140925. doi: 10.1371/journal.pone.0140925 (2015)