Evaluation of circulating tumor cells and serological cell death biomarkers in small cell lung cancer patients undergoing chemotherapy.
Lancashire, Lee J
Ward, Timothy H
Board, Ruth E
Krebs, Matthew G
Ranson, Malcolm R
Lorigan, Paul C
Blackhall, Fiona H
AffiliationClinical and Experimental Pharmacology, Paterson Institute for Cancer Research, Wilmslow Road, Manchester, M20 4BX, UK.
MetadataShow full item record
AbstractSerological cell death biomarkers and circulating tumor cells (CTCs) have potential uses as tools for pharmacodynamic blood-based assays and their subsequent application to early clinical trials. In this study, we evaluated both the expression and clinical significance of CTCs and serological cell death biomarkers in patients with small cell lung cancer. Blood samples from 88 patients were assayed using enzyme-linked immunosorbent assays for various cytokeratin 18 products (eg, M65, cell death, M30, and apoptosis) as well as nucleosomal DNA. CTCs (per 7.5 ml of blood) were quantified using Veridex CellSearch technology. Before therapeutic treatment, cell death biomarkers were elevated in patients compared with controls. CTCs were detected in 86% of patients; additionally, CD56 was detectable in CTCs, confirming their neoplastic origin. M30 levels correlated with the percentage of apoptotic CTCs. M30, M65, lactate dehydrogenase, and CTC number were prognostic for patient survival as determined by univariate analysis. Using multivariate analysis, both lactate dehydrogenase and M65 levels remained significant. CTC number fell following chemotherapy, whereas levels of serological cell death biomarkers peaked at 48 hours and fell by day 22, mirroring the tumor response. A 48-hour rise in nucleosomal DNA and M30 levels was associated with early response and severe toxicity, respectively. Our results provide a rationale to include the use of serological biomarkers and CTCs in early clinical trials of new agents for small cell lung cancer.
CitationEvaluation of circulating tumor cells and serological cell death biomarkers in small cell lung cancer patients undergoing chemotherapy. 2009, 175 (2):808-16 Am. J. Pathol.
JournalThe American Journal of Pathology
- Prognostic impact of circulating tumor cells in patients with small cell lung cancer.
- Authors: Naito T, Tanaka F, Ono A, Yoneda K, Takahashi T, Murakami H, Nakamura Y, Tsuya A, Kenmotsu H, Shukuya T, Kaira K, Koh Y, Endo M, Hasegawa S, Yamamoto N
- Issue date: 2012 Mar
- Phenotypic characterization of circulating tumor cells in the peripheral blood of patients with small cell lung cancer.
- Authors: Messaritakis I, Politaki E, Kotsakis A, Dermitzaki EK, Koinis F, Lagoudaki E, Koutsopoulos A, Kallergi G, Souglakos J, Georgoulias V
- Issue date: 2017
- Circulating tumor cells in small-cell lung cancer: a predictive and prognostic factor.
- Authors: Hiltermann TJ, Pore MM, van den Berg A, Timens W, Boezen HM, Liesker JJ, Schouwink JH, Wijnands WJ, Kerner GS, Kruyt FA, Tissing H, Tibbe AG, Terstappen LW, Groen HJ
- Issue date: 2012 Nov
- Dynamic changes of phenotypically different circulating tumor cells sub-populations in patients with recurrent/refractory small cell lung cancer treated with pazopanib.
- Authors: Messaritakis I, Politaki E, Koinis F, Stoltidis D, Apostolaki S, Plataki M, Dermitzaki EK, Georgoulias V, Kotsakis A
- Issue date: 2018 Feb 2
- Circulating tumor cells as a predictive biomarker in patients with small cell lung cancer undergoing chemotherapy.
- Authors: Aggarwal C, Wang X, Ranganathan A, Torigian D, Troxel A, Evans T, Cohen RB, Vaidya B, Rao C, Connelly M, Vachani A, Langer C, Albelda S
- Issue date: 2017 Oct