RESULTS:
1 - 3 of 3 for ""Pgp""
Phenothiazines and Structurally Related Compounds as Modulators of Cancer Multidrug Resistance
Phenothiazines and structurally related compounds alongside their other biological activities are able to modulate multidrug resistance (MDR) in tumor cells. The extensive investigations on their MDR modulation effects consist part of the efforts to overcome MDR - the major obstacle in cancer chemotherapy. In this article we try to systematize the results collected in the last two decades in two main aspects. The first one comprises the mechanism of modulation by phenothiazine-type MDR modulators. Two main possible mechanisms of MDR reversal are reviewed: (i) direct interaction with Pgp; (ii) interactions with membrane phospholipids. The second aspect relates to the structural properties of phenothiazines and related compounds responsible for their MDR reversing effect. The structural alerts and physicochemical properties influencing anti-MDR activity are considered as identified by structure - activity (SAR) or quantitative structure - activity relationship (QSAR) studies. Results discussed in the article point to MDR modulation by phenothiazines and related compounds as a complex process in which more than one mechanism are certainly involved. Further investigations in this direction should contribute to elucidation of the possible mechanisms of MDR modulation by these compounds. On the basis of the studies discussed the potential use of phenothiazine-type MDR modulators as a model system in the further investigations of the MDR phenomenon is outlined.
PET Imaging of Multidrug Resistance in Tumors Using 18F-Fluoropaclitaxel
The failure of solid tumors to respond to chemotherapy is a complicated and clinically frustrating issue. The ability to predict which tumors will respond to treatment could reduce the human and monetary costs of cancer therapy by allowing pro-active selection of a chemotherapeutic to which the tumor does not express resistance. PET/CT imaging with a radiolabeled form of paclitaxel F-18 fluoropaclitaxel (FPAC) may be able to predict the uptake of paclitaxel in solid tumors and as a substrate of P-glycoprotein it may also predict which tumors exhibit multidrug resistance (MDR) a phenotype in which tumors fail to respond to a wide variety of chemically unrelated chemotherapeutic agents. This article reviews the synthetic preclinical and early human data obtained during the development phase of this promising new radiopharmaceutical.
Evaluating Fate of Emerging Resistance Hitting the Brakes on Conventional Treatment Approach
The tumor microenvironment of TNBC cells was associated with the induction of angiogenesis proliferation apoptosis inhibition immune suppression and drug resistance. TME creates a niche for the survival and interaction of cancer cells with surrounding cells. TME promoted epithelial to mesenchymal transition stemness and chemoresistance and ensured the escape of TNBC cells from the chemotherapeutic and immunological responses. This chapter highlighted the role of cancer stem cells hypoxia lysosomal biomass tumor-associated macrophages PTEN PI3K/Akt/mTOR pathway and ABC transporters in inducing resistance against standard therapeutic regimens. The possible role of miRNA transcriptional signatures and tumor-infiltrating lymphocytes as a predictor of chemoresistance was also depicted. The impact of drug repurposing and combinational therapeutic approach to overcome the obstacle of chemoresistance have been underlined in this chapter for the treatment of TNBC. nbsp;