Tyrosine Kinase Inhibitors Influence ABCG2 Expression in EGFR‐Positive MDCK BCRP Cells via the PI3K/Akt Signaling Pathway

  title={Tyrosine Kinase Inhibitors Influence ABCG2 Expression in EGFR‐Positive MDCK BCRP Cells via the PI3K/Akt Signaling Pathway},
  author={Anne Pick and Michael Wiese},
Multidrug resistance observed in cancer chemotherapy is commonly attributed to overexpression of efflux transporter proteins. These proteins act as ATP‐dependent drug efflux pumps, actively extruding chemotherapeutic agents from cells and causing a decrease in intracellular drug accumulation. Besides the well‐recognized role of P‐glycoprotein (P‐gp, ABCB1), the breast cancer resistance protein (BCRP, ABCG2) is becoming increasingly accepted as playing an important role in multidrug resistance… 

ABCG2/BCRP: Specific and Nonspecific Modulators

The aim of the present review is to describe and highlight specific and nonspecific modulators of ABCG2 reported to date based on the selectivity of the compounds, as many of them are effective against one or more ABC transport proteins.

Icotinib antagonizes ABCG2-mediated multidrug resistance, but not the pemetrexed resistance mediated by thymidylate synthase and ABCG2

It is shown that the up-regulation of TS in ABCG2-overexpressing cell line NCI-H460/MX20 may play a role of resistance to pemetrexate, and the findings suggested different possible strategies of overcoming the resistance of topotecan and pembrexed in the NSCLC patients.

ARRY‐334543 Reverses Multidrug Resistance by Antagonizing the Activity of ATP‐Binding Cassette Subfamily G Member 2

It is concluded that ARRY‐334543 significantly reverses drug resistance mediated by ABCG2, resulting in the elevated intracellular accumulation of chemotherapeutic drugs in theABCG2‐overexpressing cell lines.

Alectinib (CH5424802) antagonizes ABCB1- and ABCG2-mediated multidrug resistance in vitro, in vivo and ex vivo

Findings suggest that alectinib combined with traditional chemotherapy may be beneficial to patients with ABCB1- or ABCG2-mediated MDR, which is the primary cause of chemotherapy failure.

The EGFR pathway regulates BCRP expression in NSCLC cells: role of erlotinib.

The results suggest that the EGFR and Akt pathways are involved in regulation of BCRP expression, trafficking and drug transport activity and warrant future studies on the pharmacologic modulation of these pathways to enhance the efficacy of anticancer combinations of erlotinib with drugs that are B CRP transport substrates.

Poziotinib Inhibits the Efflux Activity of the ABCB1 and ABCG2 Transporters and the Expression of the ABCG2 Transporter Protein in Multidrug Resistant Colon Cancer Cells

The novel results show that poziotinib interacts with the ABCB1 and ABCG2 transporter, suggesting that poZiot inib may increase the efficacy of certain chemotherapeutic drugs used in treating MDR CRC.



The epidermal growth factor tyrosine kinase inhibitor AG1478 and erlotinib reverse ABCG2-mediated drug resistance.

It is concluded that AG1478 and erlotinib potently reverse ABCG2-mediated MDR through directly inhibiting the drug efflux function ofABCG2 in the ABCG 2-overexpressing cells.

Erlotinib (Tarceva, OSI-774) antagonizes ATP-binding cassette subfamily B member 1 and ATP-binding cassette subfamily G member 2-mediated drug resistance.

It is concluded that erlotinib reverses ABCB 1- and ABCG2-mediated MDR in cancer cells through direct inhibition of the drug efflux function of ABCB1 andABCG2.

High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter.

It is shown that certain TKIs, already in the clinical phase of drug development, directly interact with the ABCG2 multidrug transporter protein with a high affinity, and this data raises the possibility that an extrusion of TKI byMultidrug transporters, e.g.,ABCG2, may be involved in tumor cell TKI resistance.

Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2)

Observations of functional adenosine triphosphate (ATP)-dependent drug efflux in certain multidrug-resistant cancer cell lines without overexpression of P-glycoprotein or multidrug resistance protein

Imatinib Mesylate Is a Potent Inhibitor of the ABCG2 (BCRP) Transporter and Reverses Resistance to Topotecan and SN-38 in Vitro

It is shown that imatinib mesylate potently reverses ABCG2-mediated resistance to topotecan and SN-38 and significantly increases accumulation of topotECan only in cells expressing functional ABCG 2.

Lapatinib (Tykerb, GW572016) reverses multidrug resistance in cancer cells by inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member 2.

Investigation of the ability of lapatinib to reverse tumor multidrug resistance (MDR) due to overexpression of ABC subfamily B member 1 (ABCB1) and ABCsubfamily G member 2 (ABCG2) transporters found it reverses ABCB1- and ABCG2-mediated MDR by directly inhibiting their transport function.

Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter.

Evidence is provided for BCRP as a MTX-transporter using an in vitro membrane vesicle system and a possible mechanism by which it confers resistance is revealed.

Reversal of breast cancer resistance protein (BCRP/ABCG2)‐mediated drug resistance by novobiocin, a coumermycin antibiotic

It is suggested that novobiocin effectively overcomes BCRP‐mediated drug resistance at acceptable concentrations.

Potent and selective inhibitors of breast cancer resistance protein (ABCG2) derived from the p-glycoprotein (ABCB1) modulator tariquidar.

It is shown that ABCG2 inhibitors might be useful for cancer treatment with respect to reversal of multidrug resistance, overcoming the BBB and targeting of tumor stem cells.