ABC Transporters and Cancer by Toshihisa Ishikawa, John Schuetz PDF

By Toshihisa Ishikawa, John Schuetz

ISBN-10: 0128013613

ISBN-13: 9780128013618

ABC Transporters and Cancer offers precious details at the interesting and fast-moving box of melanoma study. right here, notable and unique studies are provided on quite a few issues. This quantity covers ABC transporters and melanoma, and is appropriate for researchers and scholars alike.

  • Provides info on melanoma research
  • Outstanding and unique reviews
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    2014)Vandetanib++++ElacridarFivefoldbMinocha et al. (2012a)Veliparib++++ElacridarCompleteaLin et al. (2014)Vemurafenib+++++ElacridarPartial (~ 59%)aDurmus et al. (2012) If available, effect of using pharmacological inhibitors of the ABC transporters on brain penetration is also presented. a Relative to vehicle-treated Abcb1a/1b;Abcg2−/− mice. b Data available only in WT mice where brain-to-plasma ratios were compared between elacridar- and vehicle-treated groups. 1 Drugs affected mostly by Abcb1a but also by Abcg2 in their brain accumulation For a number of those new drugs that are in vitro substrates of both Abcb1 and Abcg2, the impact of Abcb1a was predominant in restricting the brain disposition, and the contribution of Abcg2 only became apparent when Abcb1 was absent.

    The inhibited target proteins of these TKIs can also be found in Table 2. , 2009). , 2011). , 2012). Table 2 In vivo impact of Abcb1a/1b and Abcg2 on the oral availability in mice of TKIs that are known to be transported by Abcb1 and/or Abcg2 Drug nameTarget molecule(s)Impact of Abcb1a/1bImpact of Abcg2ReferencesAxitinibVEGFR, c-KIT, and PDGFR–+Poller et al. (2011)CediranibVEGF––Wang et al. (2012)CrizotinibALK+–Tang et al. (2014)CYT387JAK1/2––Durmus et al. (2013)DabrafenibBRAFOral uptake increased in absence of both transporters; individual contributions not determinedMittapalli et al.

    2010). However, since plasma and tumor concentrations of paclitaxel were not measured during these tumor growth experiments, it remains unclear if inhibition of Abcb1a/1b took place primarily in intestinal and hepatic tissue or also in tumor tissue, and thus what was the primary cause of the improved antitumor efficacy: enhanced oral availability, or also increased tumor penetration of paclitaxel. Further experimentation will be needed to resolve this matter. 2 Apical ABC transporters in the oral bioavailability of rationally designed anticancer drugs In contrast to the traditional cytotoxic drugs, which usually work against all actively dividing cells, rationally designed anticancer drugs are designed to interfere with specific molecules involved in cancer cell growth and survival.

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