Circulating Tumor Cells: A Multifunctional Biomarker

Yap, Timothy A.; Lorente, David; Omlin, Aurelius; Olmos, David; Bono, Johann S. de

doi:10.1158/1078-0432.ccr-13-2664

Cited by 183 publications

(147 citation statements)

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“…Technological advances now allow the isolation of viable CTCs, which maintain tumorigenicity when xenografted in immunocompromised mice [97][98][99] ( 98 . In patients with ER-positive breast cancer, CTCs have also proven to be a useful model to study the genetic evolution of the tumour and to identify novel drug susceptibilities 104 .…”

Section: Modelling Metastatic Disease Subcutaneous Transplantation Umentioning

confidence: 99%

Interrogating open issues in cancer precision medicine with patient-derived xenografts

et al. 2017

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Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer evolutionary dynamics during tumour progression and under drug pressure, and the mechanisms of resistance to treatment. The ability of PDX models to predict clinical outcomes is being improved through mouse humanization strategies and implementation of co-clinical trials, within which patients and PDXs reciprocally inform therapeutic decisions. This Opinion article discusses aspects of PDX modelling that are relevant to these questions and highlights the merits of shared PDX resources to advance cancer medicine from the 6 perspective of EurOPDX, an international initiative devoted to PDX-based research.Response to anticancer therapies varies owing to the substantial molecular heterogeneity of human tumours and to poorly defined mechanisms of drug efficacy and resistance 1 . Immortalized cancer cell lines, either cultured in vitro or grown as xenografts, cannot interrogate the complexity of human tumours, and only provide determinate insights into human disease, as they are limited in number and diversity, and have been cultured on plastic over decades 2 .This disconnection in scale and biological accuracy contributes considerably to attrition in drug development [3][4][5] .Surgically derived clinical tumour samples that are implanted in mice (known as patient-derived xenografts (PDXs)) are expected to better inform therapeutic development strategies. As intact tissue -in which the tumour architecture and the relative proportion of cancer cells and stromal cells are both maintained -is directly implanted into recipient animals, the alignment with human disease is enhanced. More importantly, PDXs retain the idiosyncratic characteristics of different tumours from different patients; hence, they can effectively recapitulate the intra-tumour and inter-tumour heterogeneity that typifies human cancer 6-9 . 7 Exhaustive information on the key characteristics and the practical applications of PDXs can be found in recent reviews [10][11][12][13] . In this Opinion article, we discuss basic methodological concepts, as well as challenges and opportunities in developing "next-generation" models to improve the reach of PDXs as preclinical tools for in vivo studies (TABLE 1). We also elaborate on the merits of PDXs for exploring the intrinsic heterogeneity and subclonal genetic evolution of individual tumours, and discuss how this may influence therapeutic resistance. Finally, we examine the utility of PDXs in navigating complex variables in clinical decision-making, such as the discovery of predictive and prognostic biomarkers, and the categorization of genotype-drug response correlations in high-throughput formats. Being primarily co-authored by leading members of the EurOPDX Consortium (see Further information), we provide...

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Section: Modelling Metastatic Disease Subcutaneous Transplantation Umentioning

confidence: 99%

Interrogating open issues in cancer precision medicine with patient-derived xenografts

et al. 2017

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“…This may also hold true for other malignancies. Circulating tumor cells have been detected in patients with breast cancer, head and neck cancer, non-small cell lung carcinoma, pancreatic cancer, and renal cell carcinoma, and are generally associated with poor survival (17).…”

Section: Macrophages As Effector Cells In Mab Therapymentioning

confidence: 99%

Antibody-Dependent Phagocytosis of Tumor Cells by Macrophages: A Potent Effector Mechanism of Monoclonal Antibody Therapy of Cancer

2015

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Nowadays, it is impossible to imagine modern cancer treatment without targeted therapies, such as mAbs, that bind to tumor-associated antigens. Subsequently, mAbs can use a wide range of effector functions that mostly engage the immune system. mAbs can bridge immune effector cells with tumor cells, which can result in antibody-dependent cytotoxicity. Increasing evidence, however, identified macrophages as prominent effector cells and induction of antibody-dependent cell phagocytosis as one of the primary mechanisms of action mediated by mAbs. Macrophages are extremely effective in eliminating tumor cells from the circulation. Several immunosuppressive mechanisms may, however, hamper their function, particularly in solid malignancies. In this review, we discuss the evolving insight of macrophages as effector cells in mAb therapy and address novel (co)therapeutic strategies that may be used to fully unleash their cytotoxic capacity for the treatment of cancer.Cancer Res; 75(23); 5008-13. Ó2015 AACR.

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“…Two broad methodologies for CTC detection are labelbased positive selection using tumor epithelial cell surface markers or label-independent negative selection approach based on biophysical or functional properties of CTCs (49). Label-based capture assumes that CTCs have the same phenotypic characteristics as the primary tumor.…”

Section: Detection and Analysismentioning

confidence: 99%

Non-invasive diagnostic platforms in management of non-small cell lung cancer: opportunities and challenges

Velcheti

Pennell

2017

Ann. Transl. Med.

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Several non-invasive diagnostic platforms are already being incorporated in routine clinical practice in the work up and monitoring of patients with lung cancer. These approaches have great potential to improve patient selection and monitor patients while on therapy, however several challenges exist in clinical validation and standardization of such platforms. In this review, we summarize the current technologies available for non-invasive diagnostic evaluation from the blood of patients with non-small cell lung cancer (NSCLC), and discuss the technical and logistical challenges associated incorporating such testing in clinical practice.

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Circulating Tumor Cells: A Multifunctional Biomarker

Cited by 183 publications

References 100 publications

Interrogating open issues in cancer precision medicine with patient-derived xenografts

Interrogating open issues in cancer precision medicine with patient-derived xenografts

Antibody-Dependent Phagocytosis of Tumor Cells by Macrophages: A Potent Effector Mechanism of Monoclonal Antibody Therapy of Cancer

Non-invasive diagnostic platforms in management of non-small cell lung cancer: opportunities and challenges

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