title: Autophagy facilitates the Lapatinib resistance of HER2 positive breast cancer cells.
abstract: ErbB2 receptor (HER2) tyrosine kinase was overexpressed in about 25% breast cancers, and was correlated with extremely aggressive phenotype and poor prognosis. Lapatinib, an oral, reversible inhibitor of both ErbB2 and EGFR tyrosine kinases, was approved in combination with capecitabine for treating advanced stage ErbB2 positive breast cancers. However, the clinical response of Lapatinib was seriously limited by the drug resistance. We established the Lapatinib resistant breast cancer cell lines and the preliminary data demonstrated the increased autophagosome formation in the stable resistant cells. The resistant cells were re-sensitized to Lapatinib after treated with autophagy inhibitor. According to our preliminary data and related reference, we hypothesized that autophagy could facilitate the ErbB2 positive breast cancer cells to be Lapatinib resistant and promoted the survival of the resistant cells. The abrogation of autophagy might restore the drug sensitivity. Autophagy might be one of the targets to overcome the Lapatinib resistance.
authors.affiliation: Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, ChangLe West Road #15, 710032 Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Suning
authors.initials: S
authors.lastname: Chen
authors.forename: Xiumin
authors.initials: X
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Feng
authors.forename: Ying
authors.initials: Y
authors.lastname: Chang
authors.forename: Zhirui
authors.initials: Z
authors.lastname: Wang
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D001343:Autophagy / Q000502:physiology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008954:Models, Biological; D047428:Protein Kinase Inhibitors / Q000378:metabolism* / Q000627:therapeutic use; D011799:Quinazolines / Q000378:metabolism / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human