Molecular and Pharmacological Mechanisms of Drug Resistance:An Evolving Paradigm.
The high heterogeneity and genomic instability of malignant tumors explains why even responsive tumors contain cell clones that are resistant for many possible mechanisms involving intracellular drug inactivation, low uptake or high efflux of anticancer drugs from cancer cells, qualitative or quantitative changes in the drug target. Many tumors, however, are resistant because of insufficient exposure to anticancer drugs, due to pharmacokinetic reasons and inefficient and heterogeneous tumor drug distribution, related to a deficient vascularization and high interstitial pressure. Finally, resistance can be related to the activation of anti-apoptotic and cell survival pathways by cancer cells and often enhanced by tumor microenvironment.
Department of Oncology, IRCCS 'Mario Negri', Institute for Pharmacological Research, 20145, Milan, Italy.
Benedetta
B
Colmegna
Department of Oncology, IRCCS 'Mario Negri', Institute for Pharmacological Research, 20145, Milan, Italy.
Lavinia
L
Morosi
Department of Oncology, IRCCS 'Mario Negri', Institute for Pharmacological Research, 20145, Milan, Italy. maurizio.dincalci@marionegri.it.
Maurizio
M
D'Incalci
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D019008:Drug Resistance, Neoplasm; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D059016:Tumor Microenvironment
D000970:Antineoplastic Agents
Apoptosis; Drug distribution; Mass spectrometry imaging; Multidrug resistance; Pharmacokinetics