Current and future therapeutic approaches for the treatment of small cell lung cancer

Rossi, Antonio; Tay, Rebecca; Chiramel, Jaseela; Prelaj, Arsela; Califano, Raffaele

doi:10.1080/14737140.2018.1453361

Cited by 30 publications

(27 citation statements)

References 103 publications

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“…From the therapeutic perspectives, N-Myc expression levels, the neuroendocrine-low expression profile, and variant pathohistopathology are all expected to serve as the useful biomarkers to predict the sensitivity to Aurora kinase inhibition in the clinical settings. It has been shown that Aurora kinase inhibition is highly likely to improve the chemotherapy response in vivo, which strongly suggests that the patients with N-Myc-amplified SCLCs exhibit the significant clinical benefit from the first-line therapy with Aurora kinase inhibitors in combination with the conventional chemotherapy [ 67 , 69 , 70 ]. In addition, it has been very recently shown that α subunit of the epithelial sodium channel (αENaC) is a downstream therapeutic target molecule of ASCL1-positive in pulmonary neuroendocrine tumor [ 71 – 73 ].…”

Section: Emerging Roles Of Myc In Terms Of the Carcinogensis Of The Dmentioning

confidence: 99%

Emerging roles of Myc in stem cell biology and novel tumor therapies

Yoshida

2018

J Exp Clin Cancer Res

183

154

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The pathophysiological roles and the therapeutic potentials of Myc family are reviewed in this article. The physiological functions and molecular machineries in stem cells, including embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, are clearly described. The c-Myc/Max complex inhibits the ectopic differentiation of both types of artificial stem cells. Whereas c-Myc plays a fundamental role as a “double-edged sword” promoting both iPS cells generation and malignant transformation, L-Myc contributes to the nuclear reprogramming with the significant down-regulation of differentiation-associated genetic expression. Furthermore, given the therapeutic resistance of neuroendocrine tumors such as small-cell lung cancer and neuroblastoma, the roles of N-Myc in difficult-to-treat tumors are discussed. N-Myc-driven neuroendocrine tumors tend to highly express NEUROD1, thereby leading to the enhanced metastatic potential. Importantly enough, accumulating evidence strongly suggests that c-Myc can be a promising therapeutic target molecule among Myc family in terms of the biological characteristics of cancer stem-like cells (CSCs). The presence of CSCs leads to the intra-tumoral heterogeneity, which is mainly responsible for the therapeutic resistance. Mechanistically, it has been shown that Myc-induced epigenetic reprogramming enhances the CSC phenotypes. In this review article, the author describes two major therapeutic strategies of CSCs by targeting c-Myc; Firstly, Myc-dependent metabolic reprogramming is closely related to CD44 variant-dependent redox stress regulation in CSCs. It has been shown that c-Myc increases NADPH production via enhanced glutaminolysis with a finely-regulated mechanism. Secondly, the dormancy of CSCs due to FBW7-depedent c-Myc degradation pathway is also responsible for the therapeutic resistance to the conventional anti-tumor agents, the action points of which are largely dependent on the operation of the cell cycle. That is why the loss-of-functional mutations of FBW7 gene are expected to trigger “awakening” of dormant CSCs in the niche with c-Myc up-regulation. Collectively, although the further research is warranted to develop the effective anti-tumor therapeutic strategy targeting Myc family, we cancer researchers should always catch up with the current advances in the complex functions of Myc family in highly-malignant and heterogeneous tumor cells to realize the precision medicine.

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Section: Emerging Roles Of Myc In Terms Of the Carcinogensis Of The Dmentioning

confidence: 99%

Emerging roles of Myc in stem cell biology and novel tumor therapies

Yoshida

2018

J Exp Clin Cancer Res

183

154

View full text Add to dashboard Cite

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“…It is characterized by early and widespread metastatic dissemination and, strikingly, a remarkable response to platinum-based chemotherapy followed almost invariably by development of resistant disease. The first-line therapy for SCLC has not changed over several decades, and there is no effective second-line therapy to date ( Farago and Keane, 2018 , Koinis et al., 2016 , Rossi et al., 2018 ). Importantly, mechanisms underlying initial sensitivity and subsequent resistance of SCLC cells are not understood, and SCLC remains a recalcitrant cancer ( Ujhazy and Lindwasser, 2018 , Yang et al., 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Tumor Heterogeneity Underlies Differential Cisplatin Sensitivity in Mouse Models of Small-Cell Lung Cancer

et al. 2019

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Summary Small-cell lung cancer is the most aggressive type of lung cancer, characterized by a remarkable response to chemotherapy followed by development of resistance. Here, we describe SCLC subtypes in Mycl- and Nfib-driven GEMM that include CDH1-high peripheral primary tumor lesions and CDH1-negative, aggressive intrapulmonary metastases. Cisplatin treatment preferentially eliminates the latter, thus revealing a striking differential response. Using a combined transcriptomic and proteomic approach, we find a marked reduction in proliferation and metabolic rewiring following cisplatin treatment and present evidence for a distinctive metabolic and structural profile defining intrinsically resistant populations. This offers perspectives for effective combination therapies that might also hold promise for treating human SCLC, given the very similar response of both mouse and human SCLC to cisplatin.

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“…Radiotherapy plays a major role in the management of lung cancer. 27 Previous studies have shown the effect of radiation on heart diseases. 20,[28][29][30] In the present study, both the SXscore and the SXhigh percentage were greater in the radiotherapy group in relation to the non-radiotherapy group.…”

Section: Discussionmentioning

confidence: 99%

Ablação por Cateter sem Uso de Raios X para Tratamento de Fibrilação Atrial e Arritmias Atriais

Zimerman

2020

Arquivos Brasileiros De Cardiologia

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Background: Chemotherapy-related coronary artery disease (CAD) is becoming an emerging issue in clinic. However, the underlying mechanism of chemotherapy-related CAD remains unclear. Objective: The study investigated the association between chemotherapy and atherosclerotic anatomical abnormalities of coronary arteries among lung cancer patients.Methods: Patients undergoing coronary angiography (CAG) between 2010 and 2017, who previously had lung cancer, were examined. Risk factors associated with CAD and information about lung cancer were evaluated. We assessed coronary-artery abnormalities by SYNTAX score (SXscore) based on CAG. In logistic-regression analysis, we defined high SXscore (SXhigh) grade as positive if ≥22. Data were analyzed through descriptive statistics and regression analysis.Results: A total of 94 patients were included in the study. The SXscore was higher in the chemotherapy group than in the non-chemotherapy group (25.25, IQR [4.50-30.00] vs. 16.50, IQR [ 5.00-22.00], p = 0.0195). The SXhigh rate was greater in the chemotherapy group than in the non-chemotherapy group (58.33% vs. 25.86; p = 0.0016). Both univariate (OR:4.013; 95% CI:1.655-9.731) and multivariate (OR:5.868; 95% CI:1.778-19.367) logistic-regression analysis revealed that chemotherapy increased the risk of greater SXhigh rates. Multivariate stepwise logistic-regression analysis showed the risk of more severe anatomical CAD is increased by chemotherapy as a whole by 5.323 times (95% CI: 2.002-14.152), and by platinum-based regimens by 5.850 times (95% CI: 2.027-16.879). Conclusions: Chemotherapy is associated with anatomical complexity and severity of CAD, which might partly account for the higher risk of chemotherapy-related CAD among lung cancer patients. (Arq Bras Cardiol. 2020; 114(6):1004-1012)

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Current and future therapeutic approaches for the treatment of small cell lung cancer

Cited by 30 publications

References 103 publications

Emerging roles of Myc in stem cell biology and novel tumor therapies

Emerging roles of Myc in stem cell biology and novel tumor therapies

Tumor Heterogeneity Underlies Differential Cisplatin Sensitivity in Mouse Models of Small-Cell Lung Cancer

Ablação por Cateter sem Uso de Raios X para Tratamento de Fibrilação Atrial e Arritmias Atriais

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