This workshop on cell and tissue PK-PD of anticancer drugs, intended for mathematicians,
biologists, pharmacologists and haemato-oncologists, comes after events organised on related
themes in March 2008: a
CEA-EDF-INRIA school on cancer modelling and a
workshop on
haematopoiesis and its disorders.
We expect presentations dealing with molecular and physiologically based PK-PD, at the single cell level
and at the level of cell populations, whole individuals and populations of patients, of mechanisms of action
of anticancer drugs. Achievements encountered in haemato-oncology rely either on combinations of
molecules with complementary effects, or on single drug therapies with multiple targets
(e.g., tyrosine kinase inhibitors) or else on immuno-conjugated drugs; but the use of these treatments is
always limited by toxicities on healthy tissues and/or by the emergence of
resistance mechanisms to the drugs.
The mechanisms of these toxicities and resistances, either genetically determined or acquired, are many:
cell drug processing enzymes, active efflux transporters, mutations of cancer cells protecting the targets,
and they may vary from one subject to the other (genetic polymorphism) and from one hour to another
within the 24 h span within a given subject (influence of circadian
molecular clocks on PK-PD).
Mathematical models based on ordinary or partial differential equations, for drug action mechanisms
and for the dynamics of cell populations, exist, and give a theoretical frame for the optimisation of synergies
between drugs acting on different targets. The parameters of these equations, that describe the evolution
dynamics of drug concentrations, proteins and their messenger RNAs, must be fit to within- and
between-individual variations by experiments in cell cultures, on animal
models, and by clinical data analysis.
The multi-scale aspect of molecular interactions (from molecular targets to therapeutic response), and
the hidden nature of most parameters governing their dynamics, make necessary close exchanges between
modellers, experimentalists and haemato-oncologists.
It is the aim of this workshop to foster such exchanges
and interdisciplinary collaborations to optimise therapeutics in
haematology and oncology.