Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts

Journal of Translational Medicine

Ming-Chung Jiang²  Yen-Chou Chen¹  Kao-Hui Liu¹  Szu-Ying Chin¹  Jonathan Te-Peng Tseng¹  Chia-Lun Chou²  Yi-Hsien Shih¹  Shing-Chuan Shen¹  Woan-Ruoh Lee¹ 

[1] Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan;Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, No. 252 Wu-Hsing St., Taipei 11031, Taiwan

关键词: Targeted therapy;    Targeted drug;    Serum;    Phospho-CSE1L;    Monitoring;    ERK1/2;   

Others  :  1212306
DOI  :  10.1186/s12967-015-0553-6

 received in 2015-01-16, accepted in 2015-05-28,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Lee et al.

【 图 表 】

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