Advances in novel molecular typing and precise treatment strategies for small cell lung cancer
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Small cell lung cancer (SCLC) is a high-grade neuroendocrine (NE) cancer characterized by high circulating tumor-cell burden and early extensive metastasis. Considering the complexity of SCLC genes and the immune microenvironment, their unique molecular heterogeneity profiles have been continuously explored. The understanding of SCLC subtypes has recently changed from traditional "classical" and "variant" types to "NE" and "non-NE" phenotypes and to the subtypes defined by major transcriptional regulators, which indicates the gradual revelation of high intratumoral heterogeneity and plasticity characteristics of SCLCs. Advances in genomics as well as the development of single-cell sequencing analysis and new preclinical models have helped investigators gain many new insights into SCLCs and the development of targeted therapy and immunotherapy strategies. This article provides an overview of changes in molecular typing, tumor heterogeneity, and plasticity and that of advances in the precise treatment of different subtypes of SCLC.Lung cancer is still a leading cause of cancer mortality in the world. The incidence of lung cancer in developed countries started to decrease mainly due to global anti-smoking campaigns. However, the incidence of lung cancer in women has been increasing in recent decades for various reasons. Furthermore, since the screening of lung cancer is not as yet very effective, clinically applicable molecular markers for early diagnosis are much required. Lung cancer in women appears to have differences compared with that in men, in terms of histologic types and susceptibility to environmental risk factors. This suggests that female lung cancer can be derived by carcinogenic mechanisms different from those involved in male lung cancer. Among female lung cancer patients, many are non-smokers, which could be studied to identify alternative carcinogenic mechanisms independent from smoking-related ones. In this paper, we reviewed molecular susceptibility markers and genetic changes in lung cancer tissues observed in female lung cancer patients, which have been validated by various studies and will be helpful to understand the tumorigenesis of lung cancer.
Genetic predisposition
Epidemiology of cancer
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Cancer immunotherapy has shown impressive anti-tumor activity in patients with advanced and early-stage malignant tumors, thus improving long-term survival. However, current cancer immunotherapy is limited by barriers such as low tumor specificity, poor response rate, and systemic toxicities, which result in the development of primary, adaptive, or acquired resistance. Immunotherapy resistance has complex mechanisms that depend on the interaction between tumor cells and the tumor microenvironment (TME). Therefore, targeting TME has recently received attention as a feasibility strategy for re-sensitizing resistant neoplastic niches to existing cancer immunotherapy. With the development of nanotechnology, nanoplatforms possess outstanding features, including high loading capacity, tunable porosity, and specific targeting to the desired locus. Therefore, nanoplatforms can significantly improve the effectiveness of immunotherapy while reducing its toxic and side effects on non-target cells that receive intense attention in cancer immunotherapy. This review explores the mechanisms of tumor microenvironment reprogramming in immunotherapy resistance, including TAMs, CAFs, vasculature, and hypoxia. We also examined whether the application of nano-drugs combined with current regimens is improving immunotherapy clinical outcomes in solid tumors.
Cancer Immunotherapy
Reprogramming
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Modulation of the tumor microenvironment is becoming an increasingly popular research topic in the field of immunotherapy, and studies regarding immune checkpoint blockades and cancer immunotherapy have pushed cancer immunotherapy to a climax. Simultaneously, the manipulation of the immune regulatory pathway can create an effective immunotherapy strategy; however, the tumor microenvironment serves an important role in suppressing the antitumor immunity by its significant heterogeneity. A number of patients with cancer do not have a good response to monotherapy approaches; therefore, combination strategies are required to achieve optimal therapeutic benefits. Targeting the tumor microenvironment may provide a novel strategy for immunotherapy, break down the resistance of conventional cancer therapy and produce the foundation for personalized precision medicine. The present review summarized the research regarding cancer immunotherapy from the perspective of how the tumor microenvironment affects the immune response, with the aim of proposing a novel strategy for cancer immunotherapy and combination therapy.
Cancer Immunotherapy
Immune checkpoint
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Cancer Biomarkers
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The tumor immune microenvironment has been a research hot spot in recent years. The cytokines and metabolites in the microenvironment can promote the occurrence and development of tumor in various ways and help tumor cells get rid of the surveillance of the immune system and complete immune escape. Many studies have shown that the existence of tumor microenvironment is an important reason for the failure of immunotherapy. The impact of the tumor microenvironment on tumor is a systematic study. The current research on this aspect may be only the tip of the iceberg, and a relative lack of integrity, may be related to the heterogeneity of tumor. This review mainly discusses the current status of glucose metabolism and lipid metabolism in the tumor microenvironment, including the phenotype of glucose metabolism and lipid metabolism in the microenvironment; the effects of these metabolic methods and their metabolites on three important immune cells Impact: regulatory T cells (Tregs), tumor-associated macrophages (TAM), natural killer cells (NK cells); and the impact of metabolism in the targeted microenvironment on immunotherapy. At the end of this article,the potential relationship between Ferroptosis and the tumor microenvironment in recent years is also briefly described.
Tumor progression
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Objective:To investigate the expression level of adrenomedulin(ADM)in lung cancer patients,the relationship be- tween ADM and the pathological type and stage of lung cancer.Methods:We determined the content of ADM in plasma of 20 healthy adults,24 non-lung cancer patients and 61 lung cancer patients by use of radioimmunoassay.Results:The content of ADM in the plasma of healthy control group was 30.25±8.12 pg/L,lung cancer group was 40.17±19.23 pg/L,there was significant difference between them(P＜0.05) ;The content of ADM in the plasma of non-lung cancer group was 27.94±6.75 pg/L,compared with lung cancer group,there was significant difference(P＜0.01 );Small cell lung cancer group compared with non-small cell lung cancer group,the content of ADM in plasma had no significant difference(P＞0.{)5) ;Ⅰ-Ⅲstage of lung cancer group compared withⅣstage group,the content of ADM in plasma had significant difference(P＜0.05).Conclusion: The expression level of ADM in plasma of lung cancer increased,the expression level of ADM was correlated with the stage of lung cancer and distant metastasis,No correlation was found between ADM level and the pathological type of lung cancer. Therefore,detecting ADM in plasma had great value in lung cancer diagnosis and staging,and provided a new way to lung cancer diagnosis.
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Cancer Immunotherapy
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Abstract Background: The tumor microenvironment (TME) has achieved remarkable results in the research of cancer progression in the past few years. it is crucial to understand the nature and function of TME in tumors because of precise treatment strategies for individual cancers having received widespread attention, including immunotherapy. The immune infiltrative profiles of neuroblastoma (NB) have not yet been completely illustrated. The purpose of this research is to analyses tumor immune cell infiltration (ICI) in the microenvironment of NB. Methods: We applied CIBERSORT and ESTIMATE algorithms to evaluate the ICI status of 438 NB samples. Three ICI models were selected and ICI scores were acquired. Subgroups with high ICI scores based on immune activation signaling pathways have better overall survival. Results: The genes of immunosuppressive glycosaminoglycan biosynthesis heparan sulfate signaling pathway were markedly enriched in the low ICI score subgroup. It was inferred that compared with low ICI NB subtypes, patients with high ICI NB subtypes were more likely to respond to immunotherapy and a better prognosis. Conclusion: Notably, our ICI scores not only provided new clinical and theoretical basis for mining NB prognostic markers related to the microenvironment, but also aided new ideas for the development of new NB precision immunotherapy methods.
Cancer Immunotherapy
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Tumor immunotherapy is considered to be a novel and promising therapy for tumors and it has recently become a hot research topic. The clinical success of tumor immunotherapy has been notable, but it has been less than totally satisfactory because tumor immunotherapy has performed poorly in numerous patients although it has shown appreciable efficacy in some patients. A minority of patients demonstrate durable responses but the majority of patients do not respond to tumor immunotherapy as the tumor immune microenvironment is different in different patients for different tumor types. The success of tumor immunotherapy may be affected by the heterogeneity of the tumor immune microenvironment and its components, as these vary widely during neoplastic progression. The deepening of research and the development of technology have improved our understanding of the complexity and heterogeneity of the tumor immune microenvironment and its components, and their effects on response to tumor immunotherapy. Therefore, investigating the tumor immune microenvironment and its components and elucidating their association with tumor immunotherapy should improve the ability to study, predict and guide immunotherapeutic responsiveness, and uncover new therapeutic targets.
Cancer Immunotherapy
Tumor progression
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