The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer

Middleton, Gary; Crack, L; Popat, Sanjay; Swanton, Charles; Hollingsworth, Simon J.; Buller, Richard E.; Walker, Ian; Carr, T. Hedley; Wherton, Dee; Billingham, Lucinda

doi:10.1093/annonc/mdv394

Cited by 66 publications

(48 citation statements)

References 32 publications

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“…It has also been shown that CTC profiles evolve as the disease progresses [49,50,51]. Conventional molecular assays only reflect the signal from the dominant clone or an average signal from all the clones, even though this may not be the most malignant CTC clone.…”

Section: Heterogeneity Of Distant Metastases: Circulating Tumour Cmentioning

confidence: 99%

Tumour Heterogeneity: The Key Advantages of Single-Cell Analysis

Gabriel

Ory

Lamoureux

et al. 2016

IJMS

160

102

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Tumour heterogeneity refers to the fact that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation and metastatic potential. This phenomenon occurs both between tumours (inter-tumour heterogeneity) and within tumours (intra-tumour heterogeneity), and it is caused by genetic and non-genetic factors. The heterogeneity of cancer cells introduces significant challenges in using molecular prognostic markers as well as for classifying patients that might benefit from specific therapies. Thus, research efforts for characterizing heterogeneity would be useful for a better understanding of the causes and progression of disease. It has been suggested that the study of heterogeneity within Circulating Tumour Cells (CTCs) could also reflect the full spectrum of mutations of the disease more accurately than a single biopsy of a primary or metastatic tumour. In previous years, many high throughput methodologies have raised for the study of heterogeneity at different levels (i.e., RNA, DNA, protein and epigenetic events). The aim of the current review is to stress clinical implications of tumour heterogeneity, as well as current available methodologies for their study, paying specific attention to those able to assess heterogeneity at the single cell level.

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Section: Heterogeneity Of Distant Metastases: Circulating Tumour Cmentioning

confidence: 99%

Tumour Heterogeneity: The Key Advantages of Single-Cell Analysis

Gabriel

Ory

Lamoureux

et al. 2016

IJMS

160

102

View full text Add to dashboard Cite

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“…The National Lung Matrix trial is non-randomized multi-arm study in the United Kingdom sponsored by University of Birmingham and Cancer Research UK (NCT02664935) (109). This study involved eight investigational arms—AZD5363 (AKT inhibitor), AZD 4547 (FGFR inhibitor), AZD2014 (mTORC1/2 inhibitor), palbocilib (CDK4/6 inhibitor; Pfizer), crizotinib, AZD9291 (third-generation EGFR inhibitor), selumetinib (MEK inhibitor) + docetaxel, and durvalumab (anti PD-L1 monoclonal antibody).…”

Section: Modern Precision Medicine Trial Designs In Nsclcmentioning

confidence: 99%

Imprecision in the Era of Precision Medicine in Non-Small Cell Lung Cancer

et al. 2017

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Over the past decade, major advances have been made in the management of advanced non-small cell lung cancer (NSCLC). There has been a particular focus on the identification and targeting of putative driver aberrations, which has propelled NSCLC to the forefront of precision medicine. Several novel molecularly targeted agents have now achieved regulatory approval, while many others are currently in late-phase clinical trial testing. These antitumor therapies have significantly impacted the clinical outcomes of advanced NSCLC and provided patients with much hope for the future. Despite this, multiple deficiencies still exist in our knowledge of this complex disease, and further research is urgently required to overcome these critical issues. This review traces the path undertaken by the different therapeutics assessed in NSCLC and the impact of precision medicine in this disease. We also discuss the areas of “imprecision” that still exist in NSCLC and the modern hypothesis-testing studies being conducted to address these key challenges.

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“…Cure rates for paediatric solid tumours have not substantially improved in the past decade with patients having recurrent disease performing particularly badly, reflecting the limitations of current approaches that employ intensive chemotherapy, surgery and radiation [2][3][4]. In adults, the stratification of patients by genetic profiling using high throughput sequencing has supported adaptive clinical trials [5,6], and there is an urgent need to translate such opportunities to the treatment of childhood disease.…”

Section: Introductionmentioning

confidence: 99%