Increasing tumor uptake of anticancer drugs with imatinib.
Solid malignancies often exhibit high interstitial fluid pressure (IFP), which causes poor uptake of anticancer drugs. While there are several mechanisms that regulate IFP in tumors, activation of platelet-derived growth factor receptor, which is expressed in various cell types within the tumor microenvironment, has been observed to play an important role in elevating IFP. In preclinical studies, treatment with imatinib, which inhibits both alpha- and beta-platelet-derived growth factor receptors, as well as KIT, ABL, ARG, and BCR-ABL tyrosine kinases, has been shown to decrease tumor IFP and concomitantly augment uptake of chemotherapeutic drugs, thereby enhancing the efficacy of chemotherapy. This review discusses preclinical studies showing the ability of imatinib to lower IFP and increase drug uptake within solid tumors, as well as the scientific rationale for clinical use of imatinib as combination therapy for chemotherapy.
Pietras
Kristian
K
University of California at San Francisco, Diabetes Center, 94143, USA.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D045604:Extracellular Fluid / Q000502:physiology*; D006801:Humans; D000068877:Imatinib Mesylate; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D010879:Piperazines / Q000627:therapeutic use*; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor