8990 in 1877. The first four authors and two lead authors contributed equally S to this work. NIH Public Access Author Manuscript Cancer Res Author manuscript, increases available in PMC 2009 Dacinostat HDAC inhibitor 1 October. Ver published in its final form: Cancer Res. First October 2008, 68: 7905 7914th doi: 10.1158/0008 5472.CAN 08 0499th PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript NIH Pr Presentation multidrug resistance is a big obstacle to successful chemotherapy is. MDR often results in the overexpression of ATP-binding cassette transporter. In the human genome, 48 different ABC transporters have been identified and are divided into seven subfamilies on sequence similarities.
So far go Ren the most important members of the ABC transporter to drug resistance in cancer cells, ABC subfamily B member 1, subfamily C ABC and ABC subfamily G member YM155 Survivin inhibitor element 2 These membrane proteins Actively pumping a variety of structurally and functionally from the amphipathic anticancer agents in tumor cells so that the intracellular Re accumulation and resulting resistance of the chemotherapeutic agent. In addition, each carrier hunter compounds additionally Tzlich unique to some substrates which translocate overlap each other. Pharmaceutical compositions comprising hydrophobic compounds transported by ABCB1, either neutral or slightly positively charged, including normal chemotherapeutic agents, like most of the periwinkle alkaloids, anthracyclines and taxanes, epipodophyllotoxins.
Some members of the subfamily ABCC has been shown to confer MDR to organic anion compounds and products of the phase II metabolism, and certain chemotherapeutic agents, natural products and nucleotide antifolates. The spectrum of chemotherapeutic drugs by ABCG2 transported includes anthracyclines, mitoxantrone, camptothecin and indolocarbazole topoisomerase I inhibitor derivatives, methotrexate and flavopiridol. To convey the ErbB / HER family of receptor tyrosine kinases transphosphorylation of tyrosine residues in the cytoplasmic Cathedral Ne of tyrosine kinase receptors via homodimerization or heterodimerization of ligand activation.
In human tumors, the epidermal growth factor and the three other members of the EGF receptor family, human epithelial type 2, 3, 4, h Overexpressed frequently or mutated say regulated, and these pathological Ver Changes in the EGFR a series of protein kinase intracellular re signaling pathways, including the Ras kinase / mitogen-activated protein kinase, phosphatidylinositol kinase 3, signal transduction and transcription, protein kinase C and phospholipase D-Kan rdern le to f growth and tumor progression, including normal F promotion of proliferation, angiogenesis, invasion, metastasis and inhibition of apoptosis. Therefore, blockade of EGFR and / or activation of Sa can 2 k Can the growth of cancer cells and suppress the progression. Lapatinib is an orally active molecule that is a small new member of the family kinase inhibitor, the tyrosine kinases EGFR and Her 2 is inhibited. In pr Clinical studies lapatinib was not against resistance to trastuzumab. In clinical studies, lapatinib in combination with capecitabine showed promising results compared to capecitabine alone in a Phase III trial of its 2-positive metastatic breast cancer whose cancer no longer responds to trastuzumab or other therapies. Lapatinib in combination with tamoxife