A novel serum protein signature associated with resistance to epidermal growth factor receptor tyrosine kinase inhibitors in head and neck squamous cell carcinoma

Box, Carol; Mendiola, Marta; Gowan, Sharon; Box, Gary; Valenti, Melanie; Brandon, Alexis de Haven; Al‐Lazikani, Bissan; Rogers, Susanne; Wilkins, Anna; Harrington, Kevin; Eccles, Suzanne A.

doi:10.1016/j.ejca.2013.03.011

Cited by 10 publications

(19 citation statements)

References 42 publications

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“…The EGFR T790M mutation has been successfully detected in serum 127 and circulating tumor cells 128 , and sequencing of EGFR , TP53 , BRAF and RAS in circulating tumor DNA has been reported 129,130 . Proteomic attempts to determine serum biomarkers that predict susceptibility and resistance to EGFR TKIs have shown some promise in lung and head and neck cancers 131,132 . In the next decade, patients who progress on an EGFR-targeted therapy may undergo circulating tumor or tumor cell DNA analysis and be paired with a therapy that is tailored to overcome resistance.…”

Section: Ongoing Research and Challengesmentioning

confidence: 99%

The quest to overcome resistance to EGFR-targeted therapies in cancer

Chong

Jänne

2013

Nat Med

904

822

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All patients with metastatic lung, colorectal, pancreatic or head and neck cancers who initially benefit from epidermal growth factor receptor (EGFR)-targeted therapies eventually develop resistance. An increasing understanding of the number and complexity of resistance mechanisms highlights the Herculean challenge of killing tumors that are resistant to EGFR inhibitors. Our growing knowledge of resistance pathways provides an opportunity to develop new mechanism-based inhibitors and combination therapies to prevent or overcome therapeutic resistance in tumors. We present a comprehensive review of resistance pathways to EGFR-targeted therapies in lung, colorectal and head and neck cancers and discuss therapeutic strategies that are designed to circumvent resistance.

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Section: Ongoing Research and Challengesmentioning

confidence: 99%

The quest to overcome resistance to EGFR-targeted therapies in cancer

Chong

Jänne

2013

Nat Med

904

822

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“…(while O 2 breathing) and sO 2 (difference in measured sO 2 between airand oxygen-breathing) decreased with tumour growth, from a 30 mm 3 volume to time of culling. The CAL R model used for this project has also been shown to be aggressive[36] and hypoxic, using MRI and histology evidence (pimonidazole for hypoxia and Hoechst staining for perfusion)[49], so a decrease in sO 2, as observed by Tomaszewski et al[41], might have been expected. However, this was not the case, either during air-or oxygen-breathing imaging, for the CAL R tumour model.The intra-and inter-tumour CoVs for the 6 day imaging study, Table A 5, were >19.3±8.7% and >27.0±4.1%, respectively, for the haemoglobin parameters (Hb, HbO 2 and HbT).…”

mentioning

confidence: 93%

“…Therefore, this study aims to obtain baseline measurements of the variation in the photoacoustic imaging measurements over the short term (<75 minutes), to investigate the potential effects of both anaesthetic duration and altering the position of the animal, as well as over the longer term (6 days), to evaluate the variations in growing tumours. The human head and neck squamous cell tumour model, CAL R , used for this study is a noncommercially available cancer cell line developed at the Institute of Cancer Research [30].…”

Section: Introductionmentioning

confidence: 99%

Quantitative photoacoustic imaging study of tumours in vivo: baseline variations in quantitative measurements

Costa

Shah

Rivens

et al. 2018

Preprint

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Photoacoustic imaging (PAI) provides information on haemoglobin levels and blood oxygenation (sO 2 ). To facilitate assessment of the variability in sO 2 and haemoglobin in tumours, for example in response to a therapy, the intrinsic variability of these parameters was evaluated in subcutaneous head and neck tumours in mice, using a PAI system (MSOT-inVision 256TF). Tumours of anaesthetized animals (midazolam-fentanyl-medetomidine)were imaged for 75 minutes; in varying positions; and repeatedly over 6 days. An increasing linear trend for tumoural haemoglobin and blood sO 2 was observed, when imaged over 75 minutes. There was no significant difference in variability of the parameters, when repositioning tumours. A negative correlation was found between tumour growth rate and percentage decrease in blood sO 2 , over 6 days. This paper shows the potential of PAI to monitor intrinsic variation and reproducibility in estimating blood sO 2 and haemoglobin, with an eventual aim of predicting and monitoring cancer treatment response.

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“…CAL S and CAL R are isogenic but CAL S is sensitive to, and CAL R resistant to EGFR tyrosine kinase inhibitors 14 . In the absence of EGF, neither cell line invaded into the BMM (Figure 3) however, as the concentration of EGF was increased (to 2.5 ng/ml), the spheroids appear to 'bud'.…”

Section: Examples Of Different Types Of Cancer Cell Invasion Are Illumentioning

confidence: 99%

Three-Dimensional (3D) Tumor Spheroid Invasion Assay

Vinci

Box

Eccles

2015

JoVE

Self Cite

173

177

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Invasion of surrounding normal tissues is generally considered to be a key hallmark of malignant (as opposed to benign) tumors. For some cancers in particular (e.g., brain tumors such as glioblastoma multiforme and squamous cell carcinoma of the head and neck -SCCHN) it is a cause of severe morbidity and can be life-threatening even in the absence of distant metastases. In addition, cancers which have relapsed following treatment unfortunately often present with a more aggressive phenotype. Therefore, there is an opportunity to target the process of invasion to provide novel therapies that could be complementary to standard anti-proliferative agents. Until now, this strategy has been hampered by the lack of robust, reproducible assays suitable for a detailed analysis of invasion and for drug screening. Here we provide a simple micro-plate method (based on uniform, self-assembling 3D tumor spheroids) which has great potential for such studies. We exemplify the assay platform using a human glioblastoma cell line and also an SCCHN model where the development of resistance against targeted epidermal growth factor receptor (EGFR) inhibitors is associated with enhanced matrix-invasive potential. We also provide two alternative methods of semiautomated quantification: one using an imaging cytometer and a second which simply requires standard microscopy and image capture with digital image analysis.

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A novel serum protein signature associated with resistance to epidermal growth factor receptor tyrosine kinase inhibitors in head and neck squamous cell carcinoma

Cited by 10 publications

References 42 publications

The quest to overcome resistance to EGFR-targeted therapies in cancer

The quest to overcome resistance to EGFR-targeted therapies in cancer

Quantitative photoacoustic imaging study of tumours in vivo: baseline variations in quantitative measurements

Three-Dimensional (3D) Tumor Spheroid Invasion Assay

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