title: Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts.
abstract: BACKGROUND
  Although targeted therapies have improved the clinical outcomes of cancer treatment, tumors resistance to targeted drug are often detected too late and cause mortality. CSE1L is secreted from tumor and its phosphorylation is regulated by ERK1/2. ERK1/2 is located downstream of various growth factor receptors and kinases, the targets of most targeted drugs. Serum phospho-CSE1L may be a marker for monitoring the efficacy of targeted therapy.
  
  
  METHODS
  We used mice tumor xenograft model to study the assay of serum phosphorylated CSE1L for early detecting the efficacy of targeted drugs. The phosphorylation status of CSE1L in vemurafenib and sorafenib treated tumor cells were assayed by immunoblotting with antibody against phosphorylated CSE1L.
  
  
  RESULTS
  Ras activation increased phospho-CSE1L expression in B16F10 melanoma cells. Vemurafenib and sorafenib treatment did not significantly reduce the total CSE1L levels; however, they inhibited ERK1/2 and CSE1L phosphorylation in A375 melanoma cells and HT-29 colorectal cancer cells. In the melanoma xenograft model, serum phospho-CSE1L level declined 5 days after vemurafenib/sunitinib treatment and 3 days after sorafenib/lapatinib treatment in the HT-29 colon cancer xenograft model. Vemurafenib/sunitinib and sorafenib/lapatinib treatments resulted in tumor regression.
  
  
  CONCLUSIONS
  Our results indicated that serum phospho-CSE1L is useful for early detecting the efficacy of targeted therapy in initial treatment and for monitoring emerging secondary drug resistance to facilitate timely therapeutic decision making.
authors.affiliation: Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan. wrlee@tmu.edu.tw.|Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, No. 252 Wu-Hsing St., Taipei, 11031, Taiwan. wrlee@tmu.edu.tw.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. wrlee@tmu.edu.tw.
authors.forename: Woan-Ruoh
authors.initials: WR
authors.lastname: Lee
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. scshen@tmu.edu.tw.
authors.forename: Shing-Chuan
authors.initials: SC
authors.lastname: Shen
authors.affiliation: Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan. shihs999@gmail.com.|Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, No. 252 Wu-Hsing St., Taipei, 11031, Taiwan. shihs999@gmail.com.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. shihs999@gmail.com.
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Shih
authors.affiliation: Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan. gallenatsou@gmail.com.|Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, No. 252 Wu-Hsing St., Taipei, 11031, Taiwan. gallenatsou@gmail.com.
authors.forename: Chia-Lun
authors.initials: CL
authors.lastname: Chou
authors.affiliation: Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan. tepengtseng@yahoo.com.tw.|Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, No. 252 Wu-Hsing St., Taipei, 11031, Taiwan. tepengtseng@yahoo.com.tw.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. tepengtseng@yahoo.com.tw.
authors.forename: Jonathan Te-Peng
authors.initials: JT
authors.lastname: Tseng
authors.affiliation: Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan. ksiksi.tw@gmail.com.|Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, No. 252 Wu-Hsing St., Taipei, 11031, Taiwan. ksiksi.tw@gmail.com.|Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. ksiksi.tw@gmail.com.
authors.forename: Szu-Ying
authors.initials: SY
authors.lastname: Chin
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. d119097017@tmu.edu.tw.
authors.forename: Kao-Hui
authors.initials: KH
authors.lastname: Liu
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. yc3270@tmu.edu.tw.
authors.forename: Yen-Chou
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan. jiangmwd@gmail.com.|Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, No. 252 Wu-Hsing St., Taipei, 11031, Taiwan. jiangmwd@gmail.com.
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D029563:Cellular Apoptosis Susceptibility Protein / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077341:Lapatinib; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D000077157:Sorafenib; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D000077210:Sunitinib; D000077484:Vemurafenib; D023041:Xenograft Model Antitumor Assays
chemical_list: D000912:Antibodies, Neoplasm; D029563:Cellular Apoptosis Susceptibility Protein; D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; D011799:Quinazolines; D013449:Sulfonamides; D000077341:Lapatinib; D000077484:Vemurafenib; D009536:Niacinamide; D000077157:Sorafenib; D048049:Extracellular Signal-Regulated MAP Kinases; D000077210:Sunitinib