Design of Adjuvant Chemotherapy Based on Target Cell Determinants of Drug Action: Possibilities and Limitations

摘要: The traditional approach to surgical adjuvant chemotherapy is select a drug or combination of drugs that have been shown be effective against advanced disease the tumor type being treated and use them in prospective randomized clinical trial. Such trials frequently involve large number patients over several years. Another conceptual discussed herein, namely attempting predict at time surgery specific sensitivity treat each patient with designed for individual. an its infancy may finally prove logistically impracticable, but appeal such this it must pursued so validity verified. At present state knowledge seems reasonable assume selective toxicity anticancer depends on multiplicity factors [3]. Indeed, action target cells determined by as (1) binding to, transport through, plasma membrane(2) activation inside cell compartment, (3) regulatory mechanisms proximal site potentially leading adaptation repair, (4) cascade changes take place result perturbation network enzymes within close metabolic pathway influence these exerted intracellular extracellular through modifications metabolite pools, (5) rate decrease active concentration cell, (6) requirements related function kinetics, (7) effects agents administered concurrently. In addition determinants operate primarily population, kinetics disposition whole body affect cellular inasmuch they determine availability time. Homeostatic hormonal influences also modify metabolism thus their drug. It is, therefore, not surprising great deal individual variability response commonly observed among same histopathologic tumor.