【摘 要】
：
Deregulated activation of tyrosine kinases plays an important role in the initiation and propagation of many hematological and solid tumors.Lapatinib is a highly selective dual inhibitor of ErbB2 (HER
【机 构】
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Duke University USA
【出 处】
：
BITs 3rd Annual World Cancer Congress-2012(2012第五届世界癌症大会)
论文部分内容阅读
Deregulated activation of tyrosine kinases plays an important role in the initiation and propagation of many hematological and solid tumors.Lapatinib is a highly selective dual inhibitor of ErbB2 (HER2) and ErbB 1 (EGFR) receptor tyrosine kinases which belongs to an important class of drugs and represent a breakthrough in the treatment of breast cancer.Unfortunately, the development of acquired resistance (autoresistance) to this important class of drugs significantly limits their efficacy in the clinic.Here we show that molecular mechanisms and biomarker strategy for the development of lapatinib and for the understanding of the development of the acquired resistance to lapatibib.The activation of RelA and the estrogen receptor (ER) by lapatinib have been identified are mechanisms contributing to the development of autoresistance.Increased RelA phosphorylation also occurred in a subset of women receiving lapatinib monotherapy,where it was associated with a poor response to therapy.Identifying mechanisms of autoresistance will provide the scientific rationale for combination therapies in clinical to treat established resistance or preferably preventing or delaying its onset altogether and by so doing, improve clinical outcomes in women with breast cancer.
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