CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients

Vroling, Laura; Lind, Joline S.W.; Haas, Richard R. de; Verheul, Henk M.W.; Hinsbergh, Victor W.M. van; Broxterman, Henk J.; Smit, Egbert F.

doi:10.1038/sj.bjc.6605477

Cited by 32 publications

(29 citation statements)

References 47 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since CECs are rare events, their precise quantification in peripheral blood (PB) samples requires a technically rigorous analytical approach, which should take many factors into consideration (8). Several pre-analytical and analytical steps significantly affect not only the quantification of CECs, but can also result in a change in the definition of these cells, leading to problems in the interpretation of the results (Table I) and in their potential association with clinical endpoints (Table II) (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34).…”

Section: Flow Cytometric Analysis Of Circulating Endothelial Cells Inmentioning

confidence: 99%

Flow cytometric analysis of circulating endothelial cells and endothelial progenitors for clinical purposes in oncology: A critical evaluation

Danova

Comolli

Manzoni

et al. 2016

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. Malignant tumors are characterized by uncontrolled cell growth and metastatic spread, with a pivotal importance of the phenomenon of angiogenesis. For this reason, research has focused on the development of agents targeting the vascular component of the tumor microenvironment and regulating the angiogenic switch. As a result, the therapeutic inhibition of angiogenesis has become an important component of anticancer treatment, however, its utility is partly limited by the lack of an established methodology to assess its efficacy in vivo. Circulating endothelial cells (CECs), which are rare in healthy subjects and significantly increased in different tumor types, represent a promising tool for monitoring the tumor clinical outcome and the treatment response. A cell population circulating into the blood also able to form endothelial colonies in vitro and to promote vasculogenesis is represented by endothelial progenitor cells (EPCs). The number of both of these cell types is extremely low and they cannot be identified using a single marker, therefore, in absence of a definite consensus on their phenotype, require discrimination using combinations of antigens. Multiparameter flow cytometry (FCM) is ideal for rapid processing of high numbers of cells per second and is commonly utilized to quantify CECs and EPCs, however, remains technically challenging since there is as yet no standardized protocol for the identification and enumeration of these rare events. Methodology in studies on CECs and/or EPCs as clinical biomarkers in oncology is heterogeneous and data have been obtained from different studies leading to conflicting conclusions. The present review presented a critical review of the issues that limit the comparability of results of the most significant studies employing FCM for CEC and/or EPC detection in patients with cancer.

show abstract

Section: Flow Cytometric Analysis Of Circulating Endothelial Cells Inmentioning

confidence: 99%

Flow cytometric analysis of circulating endothelial cells and endothelial progenitors for clinical purposes in oncology: A critical evaluation

Danova

Comolli

Manzoni

et al. 2016

Molecular and Clinical Oncology

View full text Add to dashboard Cite

show abstract

“…Multiple phase I, II, and III trials with SO alone or in combination with other chemotherapeutic drugs are ongoing. Mechanistically, SO inhibits vascular endothelial growth factor (VEGF) receptor-2 and VEGF receptor-3 expressed by endothelial cells and CD133 + circulating hematopoietic progenitor cells (15) and platelet-derived growth factor receptor-β, FLT3, Ret, and c-Kit expressed by vasculatureassociated cells and tumor cells (16,17). These kinases are involved in tumor angiogenesis, as well as in growth and progression of a variety of tumor types such as leukemias and renal cell and hepatocellular carcinomas, suggesting CSC targeting by SO.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Activity of Sorafenib and Sulforaphane Abolishes Pancreatic Cancer Stem Cell Characteristics

et al. 2010

View full text Add to dashboard Cite

Recent evidence suggests that pancreatic cancer and other solid tumors contain a subset of tumorigenic cells capable of extensive self-renewal that contribute to metastasis and treatment resistance. Sorafenib (SO) is a promising new multikinase inhibitor for treatment of advanced kidney and liver cancers. We report here targeting of pancreatic cancer stem cells (CSC) by SO and the development of a strategy to enhance this effect. Although SO administration diminished clonogenicity, spheroid formation, aldehyde dehydrogenase 1 (ALDH1) activity, growth on immunodeficient mice, proliferation, and angiogenesis and induced apoptosis, we observed SO-induced activation of NF-κB associated with survival and regrowth of spheroids. For enhanced elimination of CSC characteristics by SO, we cotreated cells with sulforaphane (SF). This broccoli isothiocyanate was recently described to eliminate pancreatic CSCs by downregulation of NF-κB activity without inducing toxic side effects. On combination treatment, SF completely eradicated SO-induced NF-κB binding, which was associated with abrogated clonogenicity, spheroid formation, ALDH1 activity, migratory capacity, and induction of apoptosis. In vivo, combination therapy reduced the tumor size in a synergistic manner. This was due to induction of apoptosis, inhibition of proliferation and angiogenesis, and downregulation of SO-induced expression of proteins involved in epithelial-mesenchymal transition. Our data suggest that SF may be suited to increase targeting of CSCs by SO. Cancer Res; 70(12); 5004-13. ©2010 AACR.

show abstract

“…Results of a biomarker analysis from a phase II trial of sorafenib plus erlotinib as first-line treatment for advanced NSCLC suggest a potential role for CD133-positive (CD133+) circulating hematopoietic progenitor cells (HPCs) for predicting response and TTP [48]. This study found that baseline levels of CD133+ HPCs were significantly lower among responders versus nonresponders (P=0.01), and values lower than the median were correlated with prolonged TTP (P=0.037).…”

Section: Multitargeted Antiangiogenic Tkismentioning

confidence: 70%

“…This study found that baseline levels of CD133+ HPCs were significantly lower among responders versus nonresponders (P=0.01), and values lower than the median were correlated with prolonged TTP (P=0.037). However, baseline CD133+ HPCs were not associated with baseline VEGF levels [48].…”

Section: Multitargeted Antiangiogenic Tkismentioning

confidence: 98%

Developmental antiangiogenic agents for the treatment of Non-Small Cell Lung Cancer (NSCLC)

Blumenschein

2011

Invest New Drugs

View full text Add to dashboard Cite

Standard therapy for advanced or metastatic non-small cell lung cancer (NSCLC) has primarily consisted of traditional cytotoxic chemotherapy, although use of targeted therapies has been approved in specific settings. Antiangiogenic agents represent a promising therapeutic strategy for treatment of advanced NSCLC. Bevacizumab is currently approved when given in combination with first-line platinum-based therapy in selected patients with nonsquamous NSCLC. Bevacizumab may also provide benefit in other clinical settings, as a part of a combination or maintenance strategy. Other antiangiogenic agents under development, including multi-targeted kinase inhibitors (MTKIs) and antibody-based agents, have exhibited mixed results in the NSCLC population. Published efficacy and safety data from clinical trials for antiangiogenic agents are reviewed, with an emphasis on novel agents and novel settings for established agents. Identification of biomarkers associated with improved efficacy may help select patients likely to receive the most benefit from these agents and may improve outcomes through development of personalized therapeutic strategies.

show abstract

CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients

Cited by 32 publications

References 47 publications

Flow cytometric analysis of circulating endothelial cells and endothelial progenitors for clinical purposes in oncology: A critical evaluation

Flow cytometric analysis of circulating endothelial cells and endothelial progenitors for clinical purposes in oncology: A critical evaluation

Synergistic Activity of Sorafenib and Sulforaphane Abolishes Pancreatic Cancer Stem Cell Characteristics

Developmental antiangiogenic agents for the treatment of Non-Small Cell Lung Cancer (NSCLC)

Contact Info

Product

Resources

About