ABSTRACT
Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1) is significantly hindering effective cancer chemotherapy. However, currently, no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically, mainly due to the inhibitor specificity, toxicity, and drug interactions. Here, we reported that three polyoxypregnanes (POPs) as the most abundant constituents of
ABSTRACT
Since the discovery that non-small cell lung cancer (NSCLC) is driven by epidermal growth factor receptor (EGFR) mutations, the EGFR tyrosine kinase inhibitors (EGFR-TKIs, e.g., gefitinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGFR-TKIs is inevitable due to various mechanisms, such as the secondary mutation (T790M), activation of alternative pathways (c-Met, HGF, AXL), aberrance of the downstream pathways (K-RAS mutations, loss of PTEN), impairment of the EGFR-TKIs-mediated apoptosis pathway (BCL2-like 11/BIM deletion polymorphism), histologic transformation, ATP binding cassette (ABC) transporter effusion, etc. Here we review and summarize the known resistant mechanisms to EGFR-TKIs and provide potential targets for development of new therapeutic strategies.
ABSTRACT
Multidrug resistance-associated protein 1 (MRP1/ABCC1) is the first identified member of ABCC subfamily which belongs to ATP-binding cassette (ABC) transporter superfamily.It is ubiquitously expressed in almost all human tissues and transports a wide spectrum of substrates including drugs,heavy metal anions,toxicants,and conjugates of glutathione,glucuronide and sulfate.With the advance of sequence technology,many MRP1/ABCC1 polymorphisms have been identified.Accumulating evidences show that some polymorphisms are significantly associated with drug resistance and disease susceptibility.In vitro reconstitution studies have also unveiled the mechanism for some polymorphisms.In this review,we present recent advances in understanding the role and mechanism of MRP1/ABCC1 polymorphisms in drug resistance,toxicity,disease susceptibility and severity,prognosis prediction,and methods to select and predict functional polymorphisms.
ABSTRACT
Multi-drug resistance(MDR) is the most frequent reason for tumor chemotherapeutic failure.ATP binding cassette(ABC) drug transporters play an important role in tumor MDR.ABCC1 is one of the members of ABC transporter super-family,which lead to drug risistance via discarding drug out of cell or changing the drug distribution in a cell.In this article,we reviewed the advance in MDR mediated by ABCC1 and its reverse.