This review aims at presenting a
synoptic, if not exhaustive, point of view on some of the problems
encountered by biologists and physicians who deal with natural
cell proliferation and disruptions of its physiological control in
cancer disease. It also aims at suggesting how mathematicians are
naturally challenged by these questions and how they might help,
not only biologists to deal theoretically with biological
complexity, but also physicians to optimise therapeutics, on which
last point the focus will be set here. To this purpose,
mathematical modelling should represent proliferating cell
population dynamics with natural built-in control targets (which
implies modelling the cell division cycle), together with the
distribution of drugs in the organism and their molecular actions
on different targets at the cell level on proliferation, i.e.,
molecular pharmacokinetics-pharmacodynamics of antiproliferative
drugs. This should make possible optimal control of drug delivery
with constraints to be determined according to the main
pharmacological issues encountered in the clinic: unwanted toxic
side-effects, occurrence of drug resistance. Mathematical
modelling should also take into account physiological determinants
of cell and tissue proliferation, such as intervention of the
immune system, circadian control on cell cycle checkpoint
proteins, and activity of intracellular drug processing enzymes
together with individual variations in the activities of these
proteins (genetic polymorphism). Taking these points into account
will add to the rich scenery of normal or disrupted cell and
tissue regulations, and their corrections by drugs, a natural
environmental, whole body physiological, frame. It is necessary
indeed to consider such a framework if one wants to eventually be
actually helpful to clinicians who routinely treat by combinations
of drugs living Humans with their complex whole body regulations,
often dependent on genotypic variations, and not isolated cells or
tissues.