Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

Turner, Natalie; Pestrin, Marta; Galardi, Francesca; Luca, Francesca De; Malorni, Luca; Leo, Angelo Di

doi:10.3390/cancers6020684

Cited by 25 publications

(22 citation statements)

References 90 publications

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“…Changing biomarker status, particularly ER and HER2, commonly occurs in advanced breast cancer [27,28] and has been previously recognised in CTCs [29][30][31][32], but there is little evidence on how to approach this in the clinic. Several trials are assessing the benefit of targeting newly-acquired receptor positivity in CTCs.…”

Section: Treating Newly Acquired Biomarkersmentioning

confidence: 97%

Circulating Tumour Cells as Liquid Biopsy in Breast Cancer—Advancing from Prognostic to Predictive Potential

Hart

Galardi

Luca

et al. 2015

Curr Breast Cancer Rep

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Circulating tumour cells (CTCs) in breast cancer offer a unique opportunity to sample tissue that can derive from multiple sites in the body and may be more representative of the whole disease than a single standard biopsy. Their presence is now clearly associated with worse prognosis and can indicate treatment failure. Improved techniques to isolate single CTCs have also permitted in-depth molecular studies, revealing marked heterogeneity. Whilst giving a novel window into tumour evolution and resistance, it also raises new questions regarding treatment approaches. The ongoing challenge remains the translation of new information gleaned from CTCs into clinical benefit.

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Section: Treating Newly Acquired Biomarkersmentioning

confidence: 97%

Circulating Tumour Cells as Liquid Biopsy in Breast Cancer—Advancing from Prognostic to Predictive Potential

Hart

Galardi

Luca

et al. 2015

Curr Breast Cancer Rep

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“…In fact, testing the status of these proteins via tissue-based assay is now the standard of care in all newly diagnosed breast cancer patients. Despite this, there exists a continued need for new biomarkers in breast cancer in order to better stratify patients for therapeutic regimens and improve outcomes 23,24…”

Section: The Urokinase Plasminogen Activator (Upa) Systemmentioning

confidence: 99%

Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors

Roy

Walsh

2014

BCTT

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The extracellular matrix (ECM) is the complex network of proteins that surrounds cells in multicellular organisms. Due to its diverse nature and composition, the ECM has a multifaceted role in both normal tissue homeostasis and pathophysiology. It provides structural support, segregates tissues from one another, and regulates intercellular communication. Furthermore, the ECM sequesters a wide range of growth factors and cytokines that may be released upon specific and well-coordinated cues. Regulation of the ECM is performed by the extracellular proteases, which are tasked with cleaving and remodeling this intricate and diverse protein matrix. Accordingly, extracellular proteases are differentially expressed in various tissue types and in many diseases such as cancer. In fact, metastatic dissemination of tumor cells requires degradation of extracellular matrices by several families of proteases, including metalloproteinases and serine proteases, among others. Extracellular proteases are emerging as strong candidate cancer biomarkers for aiding and predicting patient outcome. Not surprisingly, inhibition of these protumorigenic enzymes in animal models of metastasis has shown impressive therapeutic effects. As such, many of these proteolytic inhibitors are currently in various phases of clinical investigation. In addition to direct approaches, aberrant expression of extracellular proteases in disease states may also facilitate the selective delivery of other therapeutic or imaging agents. Herein, we outline extracellular proteases that are either bona fide or probable prognostic markers in breast cancer. Furthermore, using existing patient data and multiple robust statistical analyses, we highlight several extracellular proteases and associated inhibitors (eg, uPA, ADAMs, MMPs, TIMPs, RECK) that hold the greatest potential as clinical biomarkers. With the recent advances in high-throughput technology and targeted therapies, the incorporation of extracellular protease status in breast cancer patient management may have a profound effect on improving outcomes in this deadly disease.

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“…Although this report involved only a few patients, future studies may be able to unlock the CTC-targeting signatures for metastasis to specific secondary sites. Such information could prove to be more useful than biopsies in predicting metastatic disease, especially site-specific metastases, and eventually preventing metastases from forming and treating the metastases that have formed (86,87).…”

Section: Cell Membranes and The Invasive Phenotypementioning

confidence: 99%

“…86). Enumeration of CTC and typing CTC biomarkers are being developed to assess risk of metastatic disease and hopefully predict the effects of therapy to prevent metastases (87). CTC are thought to be directly related to stem cells, the presumptive source of metastases, so Zhang and colleagues (88) isolated CTC from patients with breast cancer without brain metastases, grew them in culture, and subjected them to metastasis assays in immunosuppressed mice.…”

Section: Cell Membranes and The Invasive Phenotypementioning

confidence: 99%

Cell Membrane Fluid–Mosaic Structure and Cancer Metastasis

Nicolson

2015

Cancer Research

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Cancer cells are surrounded by a fluid-mosaic membrane that provides a highly dynamic structural barrier with the microenvironment, communication filter and transport, receptor and enzyme platform. This structure forms because of the physical properties of its constituents, which can move laterally and selectively within the membrane plane and associate with similar or different constituents, forming specific, functional domains. Over the years, data have accumulated on the amounts, structures, and mobilities of membrane constituents after transformation and during progression and metastasis. More recent information has shown the importance of specialized membrane domains, such as lipid rafts, protein-lipid complexes, receptor complexes, invadopodia, and other cellular structures in the malignant process. In describing the macrostructure and dynamics of plasma membranes, membraneassociated cytoskeletal structures and extracellular matrix are also important, constraining the motion of membrane components and acting as traction points for cell motility. These associations may be altered in malignant cells, and probably also in surrounding normal cells, promoting invasion and metastatic colonization. In addition, components can be released from cells as secretory molecules, enzymes, receptors, large macromolecular complexes, membrane vesicles, and exosomes that can modify the microenvironment, provide specific cross-talk, and facilitate invasion, survival, and growth of malignant cells. Cancer Res; 75(7); 1169-76. Ó2015 AACR.

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Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

Cited by 25 publications

References 90 publications

Circulating Tumour Cells as Liquid Biopsy in Breast Cancer—Advancing from Prognostic to Predictive Potential

Circulating Tumour Cells as Liquid Biopsy in Breast Cancer—Advancing from Prognostic to Predictive Potential

Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors

Cell Membrane Fluid–Mosaic Structure and Cancer Metastasis

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