| Literature DB >> 21540235 |
Marc Damelin1, Kenneth G Geles, Maximillian T Follettie, Ping Yuan, Michelle Baxter, Jonathon Golas, John F DiJoseph, Maha Karnoub, Shuguang Huang, Veronica Diesl, Carmen Behrens, Sung E Choe, Carol Rios, Janet Gruzas, Latha Sridharan, Maureen Dougher, Arthur Kunz, Philip R Hamann, Deborah Evans, Douglas Armellino, Kiran Khandke, Kimberly Marquette, Lioudmila Tchistiakova, Erwin R Boghaert, Robert T Abraham, Ignacio I Wistuba, Bin-Bing S Zhou.
Abstract
Poorly differentiated tumors in non-small cell lung cancer (NSCLC) have been associated with shorter patient survival and shorter time to recurrence following treatment. Here, we integrate multiple experimental models with clinicopathologic analysis of patient tumors to delineate a cellular hierarchy in NSCLC. We show that the oncofetal protein 5T4 is expressed on tumor-initiating cells and associated with worse clinical outcome in NSCLC. Coexpression of 5T4 and factors involved in the epithelial-to-mesenchymal transition were observed in undifferentiated but not in differentiated tumor cells. Despite heterogeneous expression of 5T4 in NSCLC patient-derived xenografts, treatment with an anti-5T4 antibody-drug conjugate resulted in complete and sustained tumor regression. Thus, the aggressive growth of heterogeneous solid tumors can be blocked by therapeutic agents that target a subpopulation of cells near the top of the cellular hierarchy.Entities:
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Year: 2011 PMID： 21540235 DOI： 10.1158/0008-5472.CAN-10-3919
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701