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您的检索式：作者名="Kenneth K.W.To"
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| 1 | Olmutinib(HM61713) reversed multidrug resistance by inhibiting the activity of ATPbinding cassette subfamily G member 2 in vitro and in vivo显示文摘Overexpressing of ATP-binding cassette(ABC) transporters is the essential cause of multidrug resistance(MDR), which is a significant hurdle to the success of chemotherapy in many cancers.Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR.Olmutinib is an epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI), which has been approved in South Korea for advanced EGFR T790 M-positive non-small cell lung cancer(NSCLC). Here,we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore, olmutinib could also increase the retention of doxorubicin(DOX) and rhodamine 123(Rho 123) in ABC transporter subfamily G member 2(ABCG2)-overexpressing cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit photolabeling of ABCG2 with [^(125) I]-iodoarylazidoprazosin(IAAP). However, olmutinib neither altered ABCG2 expression at protein and m RNA levels nor blocked EGFR, Her-2 downstream signaling of AKT and ERK. Importantly,olmutinib enhanced the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth. All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug accumulation. Our findings encouraged to further clinical investigation on combination therapy of olmutinib with conventional chemotherapeutic drugs in ABCG2-overexpressing cancer patients. | Zhiqiang Zhang Xiaoran Guo Kenneth K.W.To Zhen Chen Xiaona Fang Min Luo Chunling Ma Jianhua Xu Shirong Yan Liwu Fu | 2018 | Acta Pharmaceutica Sinica B2018，8，4： | 9 |
| 2 | Exosome secretion from hypoxic cancer cells reshapes the tumor microenvironment and mediates drug resistance显示文摘Hypoxia is a common phenomenon in solid tumors as the poorly organized tumor vasculature cannot fulfill the increasing oxygen demand of rapidly expanding tumors.Under hypoxia,tumor cells reshape their microenvironment to sustain survival,promote metastasis,and develop resistance to therapy.Exosomes are extracellular vesicles secreted by most eukaryotic cells,including tumor cells.They are enriched with a selective collection of nucleic acids and proteins from the originating cells to mediate cell-to-cell communication.Accumulating evidence suggests that exosomes derived from tumor cells play critical roles in modulating the tumor microenvironment(TME).Hypoxia is known to stimulate the secretion of exosomes from tumor cells,thereby promoting intercellular communication of hypoxic tumors with the surrounding stromal tissues.Exosome-mediated signaling pathways under hypoxic conditions have been reported to cause angiogenesis,invasion,metastasis,drug resistance,and immune escape.Recently,the programmed cell death ligand-1(PD-L1)has been reported to reside as a transmembrane protein in tumor exosomes.Exosomal PD-L1 was shown to suppress T cell effector function in the TME and cause drug resistance to immune checkpoint therapy.This review provides an update about the pivotal role of tumor-derived exosomes in drug resistance to chemotherapy and immunotherapy,particularly under hypoxic conditions.Emerging strategies that target the exosomes in the hypoxic TME to enhance the antitumor efficacy are discussed. | Kenneth K.W.To William C.S.Cho | 2022 | Cancer Drug Resistance2022，5，3： | 0 |
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