Neuroendocrine Tumors of the Lung

Stamatis, Georgios

doi:10.1016/j.thorsurg.2014.05.004

Cited by 9 publications

(3 citation statements)

References 88 publications

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“…Despite an initial high response rate, tumors relapse early and are not amenable to effective further therapy. Progress of research on SCLC is hampered by availability of tumor material, as in extended disease no material is collected after initial confirmation of the diagnosis by fine-needle biopsies [ 4 ]. Alternatively, so-called liquid biopsies consist of the detection of circulating genetic material or enrichment of the diversified circulating tumor cells (CTCs) using blood samples [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Receptor tyrosine kinase expression of circulating tumor cells in small cell lung cancer

et al. 2015

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Small cell lung cancer (SCLC) has a poor prognosis and is found disseminated at first presentation in the majority of cases. The cell biological mechanisms underlying metastasis and drug resistance are not clear. SCLC is characterized by high numbers of circulating tumor cells (CTCs) and we were able to expand several CTC lines ex vivo and to relate chitinase-3-like-1/YKL-40 (CHI3L1) as marker. Availability of expanded SCLC CTC cells allowed for a screening of receptor tyrosine kinases (RTKs) expressed. The metastatic CHI3L1-negative SCLC cell line SCLC26A, established from a pleural effusion was used for comparison. The CTC cell line BHGc10 was found to exhibit increased expression of RYK, AXL, Tie-1, Dtk, ROR1/2, several ephrins (Eph) and FGF/EGF receptors compared to SCLC26A. All of these RTKs have been associated with cell motility, invasion and poor prognosis in diverse cancer entities without knowledge of their association with CTCs. The identification of RYK, AXL and ROR1/2 as pseudokinases, lacking activity, seems to be related to the observed failure of RTK inhibitors in SCLC. These kinases are involved in the noncanonical WNT pathway and their expression in SCLC CTCs represents a cancer stem cell-like phenotype.

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Section: Introductionmentioning

confidence: 99%

Receptor tyrosine kinase expression of circulating tumor cells in small cell lung cancer

et al. 2015

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“…Lung cancer is the leading cause of cancer-related deaths worldwide and, in particular, small cell lung cancer (SCLC) constitutes a highly aggressive variant accounting for approximately 15% of cases [ 1 - 3 ]. This tumor entity is characterized by early dissemination and, therefore, the majority of patients is not eligible for surgical treatment and is treated by systemic chemotherapy [ 4 ]. Despite excellent initial response rates to platinum-based combination chemotherapy patients relapse within approximately one year and are not amenable to further effective therapy [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

How to target small cell lung cancer

2015

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Small cell lung cancer (SCLC) is a highly malignant disease with dismal prognosis. Although great progress has been made in investigating genetic aberrations and putative drivers of this tumor entity, the mechanisms of rapid dissemination and acquisition of drug resistance are not clear. The majority of SCLC cases are characterized by inactivation of the tumor suppressors p53 and retinoblastoma (Rb) and, therefore, interchangeable drivers will be difficult to target successfully. Access to pure cultures of SCLC circulating tumor cells (CTCs) and study of their tumor biology has revealed a number of new potential targets. Most important, expression of chitinase-3-like-1/YKL-40 (CHI3L1) which controls expression of vascular epithelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP9) was newly described in these cells. The process switching CHI3L1-negative SCLC cells to CHI3L1-positive CTCs seems to be associated with cytokines released by inflammatory immune cells. Furthermore, these CTCs were found to promote monocyte-macrophage differentiation, most likely of the M2 tumor-promoting type, recently described to express PD-1 immune checkpoint antigen in SCLC. In conclusion, dissemination of SCLC seems to be linked to conversion of regular tumor cells to highly invasive CHI3L1-positive CTCs, which are protected by immune system suppression. Besides the classical targets VEGF, MMP-9 and PD-1, CHI3L1 constitutes a new possibly drugable molecule to retard down dissemination of SCLC cells, which may be similarly relevant for glioblastoma and other tumor entities.

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“…In 2015, the World Health Organization (WHO) classified it as neuroendocrine tumor along with typical carcinoid, atypical carcinoid and small-cell lung cancer (SCLC) (Travis et al 2015 ). LCNEC and SCLC share many similar clinicopathological features and are categorized as high-grade neuroendocrine carcinoma, which is characterized by highly aggressiveness, poor histologic differentiation, poor prognosis, susceptibility to metastasis and often at advanced stage at the time of diagnosis (Stamatis 2014 ; Ferlay et al 2015 ). The most common metastasis site is the lung, however, some patients involve not only one organ, and the prognosis often varies across metastasis sites (Chen et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Metastasis pattern and prognosis of large cell neuroendocrine carcinoma: a population-based study

Jiang¹,

Sun²,

Li³

et al. 2023

J Cancer Res Clin Oncol

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Purpose As a rare type of tumor, the metastasis pattern of large cell neuroendocrine carcinoma (LCNEC) is still unclear. Our aim was to investigate metastatic patterns and develop a predictive model of prognosis in patients with advanced LCNEC. Methods Patients of LCNEC diagnosed between 2010–2015 from the Surveillance, Epidemiology and End Results (SEER) database were retrospectively included. Chi-square test was used for baseline characteristics analysis. Survival differences were assessed using Kaplan–Meier curves. Independent prognostic factors identified by multivariate Cox proportional risk model were used for the construction of nomogram. Results 557 eligible patients with metastasis LCNEC (median (IQR), 64 (56 to 72) years; 323 males) were included in this research. Among patients with isolated metastases, brain metastases had the highest incidence (29.4%), and multisite metastases had worse OS (HR: 2.020: 95% CI 1.413–2.888; P < 0.001) and LCSS (HR: 2.144, 95% CI 1.480–3.104; P < 0.001) in all age groups. Independent prognostic indicators including age, race, T stage, N stage, chemotherapy, radiotherapy and metastatic site were used for the construction of nomogram. Concordance index (C-index) and decision-curve analyses (DCAs) showed higher accuracy and net clinical benefit of nomogram compared to the 7th TNM staging system (OS: 0.692 vs 0.555; P < 0.001; LCSS: 0.693 vs 0.555; P < 0.001). Conclusions We firstly established a novel comprehensive nomogram to predict the prognosis of metastasis LCNEC. The prognostic model demonstrated excellent accuracy and predictive performance. Chemotherapy and metastasis pattern were the two strongest predictive variables. Close follow-up of patients with LCNEC is necessary to make individualized treatment decisions according to different metastasis patterns.

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Neuroendocrine Tumors of the Lung

Cited by 9 publications

References 88 publications

Receptor tyrosine kinase expression of circulating tumor cells in small cell lung cancer

Receptor tyrosine kinase expression of circulating tumor cells in small cell lung cancer

How to target small cell lung cancer

Metastasis pattern and prognosis of large cell neuroendocrine carcinoma: a population-based study

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