EGFR and HER3 expression in circulating tumor cells and tumor tissue from non-small cell lung cancer patients

Scharpenseel, Heather; Hanssen, Annkathrin; Loges, Sonja; Mohme, Malte; Bernreuther, Christian; Peine, Sven; Lamszus, Katrin; Goy, Y.; Petersen, Cordula; Westphal, Manfred; Glatzel, Markus; Riethdorf, Sabine; Pantel, Klaus; Wikman, Harriet

doi:10.1038/s41598-019-43678-6

Cited by 85 publications

(66 citation statements)

References 35 publications

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“…In NSCLC, HER3-overexpression has been reported in 80% of EGFR-mutated adenocarcinomas [ 78 ]. HER3-DXd demonstrated to inhibit tumor growth in HER3+, EGFR-mutated, EGFR-TKI resistant patient-derived xenograft (PDX) models, while it was ineffective in HER3-negative models [ 79 ].…”

Section: Promising New Targets Under Investigationmentioning

confidence: 99%

Antibody–drug conjugates in solid tumors: a look into novel targets

2021

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Antibody–drug conjugates (ADCs) are a relatively new class of anticancer agents designed to merge the selectivity of monoclonal antibodies with cell killing properties of chemotherapy. They are commonly described as the “Trojan Horses” of therapeutic armamentarium, because of their capability of directly conveying cytotoxic drug (payloads) into the tumor space, thus transforming chemotherapy into a targeted agent. Three novel ADCs have been recently approved, i.e., trastuzumab deruxtecan, sacituzumab govitecan and enfortumab vedotin, respectively, targeting HER2, Trop2 and Nectin4. Thanks to progressive advances in engineering technologies these drugs rely on, the spectrum of diseases sensitive to these drugs as well as their indications are in continuous expansion. Several novel ADCs are under evaluation, exploring new potential targets along with innovative payloads. This review aims at providing a summary of the technology behind these compounds and at presenting the latest ADCs approved in solid tumors, as well as at describing novel targets for ADCs under investigation and new strategies to optimize their efficacy in solid tumors.

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Section: Promising New Targets Under Investigationmentioning

confidence: 99%

Antibody–drug conjugates in solid tumors: a look into novel targets

2021

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“…Several studies demonstrated that these proteins are upregulated in metastatic tissue and in CTCs compared to the primary tumor [9]. The authors concluded that the combination of EGFR/HER3 enrichment with the EpCAM-based CellSearch technique may detect a significantly higher number of CTCs in NSCLC patients by liquid biopsy [10].…”

Section: Circulating Tumor Cellsmentioning

confidence: 99%

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

Rijavec

Coco

Genova

et al. 2019

Cancers

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Non-small cell lung cancer is one leading cause of death worldwide, and patients would greatly benefit from an early diagnosis. Since targeted and immunotherapies have emerged as novel approaches for more tailored treatments, repeated assessments of the tumor biology have become pivotal to drive clinical decisions. Currently, tumor tissue biopsy is the gold standard to investigate potentially actionable biomarkers, but this procedure is invasive and may prove inadequate to represent the whole malignancy. In this regard, liquid biopsy represents a minimally invasive and more comprehensive option for early detection and investigation of this tumor. Today, cell-free DNA is the only approved circulating marker to select patients for a targeted therapy. Conversely, the other tumor-derived markers (i.e., circulating tumor cells, miRNAs, exosomes, and tumor educated platelets) are still at a pre-clinical phase, although they show promising results for their application in screening programs or as prognostic/predictive biomarkers. The main challenges for their clinical translation are the lack of reliable cutoffs and, especially for miRNAs, the great variability among the studies. Moreover, no established tool has been approved for circulating tumor cells and exosome isolation. Finally, large prospective clinical trials are mandatory to provide evidence of their clinical utility.

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“…Such studies with the Her/EGFR-targeted capture based on heterogeneous expression in cells have been previously demonstrated. 45 Subsequently, we conducted a specificity test for FeNC−Her and FeNC−EGF in capturing positive target cells relative to control from a cell mixture in serum. For this experiment, we used samples spiked with an A549−HCC827 1:1 mixture (from 10 2 to 10 4 cells per cell line), wherein A549 was a positive control for FeNC−Her, and HCC827 was a negative control.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Magnetic Iron Nanocubes Effectively Capture Epithelial and Mesenchymal Cancer Cells

et al. 2020

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Current methods for capturing circulating tumor cells (CTCs) are based on the overexpression of cytokeratin (CK) or epithelial cell-adhesion molecule (EpCAM) on cancer cells. However, during the process of metastasis, tumor cells undergo epithelial-to-mesenchymal transition (EMT) that can lead to the loss of CK/EpCAM expression. Therefore, it is vital to develop a capturing technique independent of CK/EpCAM expression on the cancer cell. To develop this technique, it is important to identify common secondary oncogenic markers overexpressed on tumor cells before and after EMT. We analyzed the biomarker expression levels in tumor cells, before and after EMT, and found two common proteinshuman epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) whose levels remained unaffected. So, we synthesized immunomagnetic iron nanocubes covalently conjugated with antibodies of Her2 or EGFR to capture cancer cells irrespective of the EMT status. The nanocubes showed high specificity (6−9-fold) in isolating the cancer cells of interest from a mixture of cells spiked in serum. We characterized the captured cells for identifying their EMT status. Thus, we believe the results presented here would help in the development of novel strategies for capturing both primary and metastatic cancer cells from patients' blood to develop an effective treatment plan.

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EGFR and HER3 expression in circulating tumor cells and tumor tissue from non-small cell lung cancer patients

Cited by 85 publications

References 35 publications

Antibody–drug conjugates in solid tumors: a look into novel targets

Antibody–drug conjugates in solid tumors: a look into novel targets

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

Magnetic Iron Nanocubes Effectively Capture Epithelial and Mesenchymal Cancer Cells

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