Cancer is one of the most feared diseases nowadays because it is known to be difficult to cure. The main reason for this difficulty is that cancer originates from subtly modified normal human cells, which proliferate uncontrollably. The widespread drugs, used in cancer chemotherapy, are cytotoxic (cell-killing) and usually work by interfering in some way with the functioning of the cell’s DNA. Cytotoxic drugs are harmful to the rest of the body unless they are very specific to cancer cells – something difficult to achieve because the modifications that change a healthy cell into a cancerous one are rather subtle. We are actually searching for:
i) new drugs that will be more selective to cancer cells with the membrane lipids as a drug target,
ii) new strategies based on blood lipoproteins for improving pharmacokinetics of the drugs (study of the time course of drug absorption, distribution, metabolism, and excretion) in the blood stream.
We are actually developing computer simulations mostly Molecular Dynamics and quantum chemistry calculations for modeling accurately drugs but also for improving their lipid targets (plasma membranes and lipoproteins). This work is done in close collaboration with Prof. P. Couvreur’s team (équipe Nanomédicaments pour le traitement de maladies graves, Institut Galien Chateney-Malabry, France).
In this seminar, we will show how squalene based drugs could be an interesting candidate for adressing such requirements. We will present our latest results on lipoproteins simulations [1] and model membranes. Cisplatin drugs together with gemcitabin and doxorubicin drugs will be discussed.
[1] Sobot, D., et al., Conjugation of squalene to gemcitabine as unique approach exploiting endogenous lipoproteins for drug delivery. Nature Communications, 2017. 8:
p. 15678.
Laboratoire Chrono-environnement UMR CNRS 6249, Besancon