A multiscale mathematical model of avascular tumor growth to investigate the therapeutic benefit of anti-invasive agents.
With the aim of inhibiting cancer growth and reducing the risk of metastasis, pharmaceutical companies in the early 1990s developed anti-metastatic agents called inhibitors of metalloproteinases (MMPi). Despite the promising results obtained in pre-clinical studies, results of Phase III trials have been somewhat disappointing for late stage cancer patients. With the aim of mathematically investigating this therapeutic failure, we developed a mechanistically based model which integrates cell cycle regulation and macroscopic tumor dynamics. By simulating the model, we evaluated the efficacy of MMPi therapy. Simulation results predict the lack of efficacy of MMPi in advanced cancer patients. The theoretical model may aid in evaluating the efficacy of anti-metastatic therapies, thus benefiting the design of prospective clinical trials.
Ribba
B
B
Clinical Pharmacology Department, Institute for Theoretical Medicine, EA 3736, Faculty of Medicine R.T.H Laennec, University of Lyon 1, Paradin St., 69376 Lyon Cedex 08, France. ribba@upcl.univ-lyon1.fr
Saut
O
O
Colin
T
T
Bresch
D
D
Grenier
E
E
Boissel
J P
JP
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000502:physiology; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D010539:Permeability; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases