Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges.

Resistance to targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) is a significant challenge in the treatment of this disease. The mechanisms of resistance are multifactorial and include molecular target alterations and activation of alternative pathways, tumor heterogeneity and tumor microenvironment change, immune evasion, and immunosuppression. Promising strategies for overcoming resistance include the development of combination therapies, understanding the resistance mechanisms to better use novel drug targets, the identification of biomarkers, the modulation of the tumor microenvironment and so on. Ongoing research into the mechanisms of resistance and the development of new therapeutic approaches hold great promise for improving outcomes for patients with NSCLC. Here, we summarize diverse mechanisms driving resistance to targeted therapy and immunotherapy in NSCLC and the latest potential and promising strategies to overcome the resistance to help patients who suffer from NSCLC.

Tumor-derived miRNAs as tumor microenvironment regulators for synergistic therapeutic options.

MicroRNAs (miRNAs) are a class of non-coding RNAs that perform post-transcriptional gene regulation. This review focuses on the role of tumor cell-derived miRNAs in the regulation of the tumor microenvironment (TME) via receptor cell recoding, including angiogenesis, expression of immunosuppressive molecules, formation of radiation resistance, and chemoresistance. Furthermore, we discuss the potential of these molecules as adjuvant therapies in combination with chemotherapy, radiotherapy, or immunotherapy, as well as their advantages as efficacy predictors for personalized therapy. MiRNA-based therapeutic agents for tumors are currently in clinical trials, and while challenges remain, additional research on tumor-derived miRNAs is warranted, which may provide significant clinical benefits to cancer patients.

The aberrant overexpression of hsa_circ_0078607 in colorectal cancer tissues and serum and its clinical significance / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探究hsa_circ_0078607在结直肠癌组织和患者血清中的表达水平及其与结直肠癌患者临床病理特征的关系，评价其能否作为结直肠癌潜在的分子诊断标志物及治疗靶标。方法：收集2018年6月至2022年1月于柳州市人民医院胃肠外科接受结直肠癌切除手术患者的58对癌及癌旁组织标本，收集2020年1月至2022年12月于柳州市人民医院初次确诊的结直肠癌患者、结直肠息肉患者及健康人体检血清共152例；从结直肠癌差异表达circRNA谱中挑选特异性高表达的hsa_circ_0078607作为候选标志物，采用qPCR法检测其在结直肠癌细胞、组织、患者血清及结直肠息肉患者血清中的相对表达量，分析其与临床病理特征的关系。采用ROC曲线评估hsa_circ_0078607对结直肠癌及结直肠息肉的诊断价值。通过Circular RNA Interactome数据库预测与hsa_circ_0078607结合的miRNA，并用Cytoscape 3.9.1软件构建circRNA-miRNA-mRNA调控网络，同时通过GO/KEGG富集分析进一步了解其功能。结果：与癌旁组织或健康人血清相比，hsa_circ_0078607在结直肠癌细胞、组织和血清及息肉患者血清中呈高表达（P<0.001），其中有52例（89.7%）患者癌组织中表达上调，6例（10.3%）表达下调。结直肠癌组织中hsa_circ_0078607的相对表达量与肿瘤位置（P=0.029）、分化程度（P=0.046）和远处转移（P=0.043）有关联。ROC结果显示，在结直肠癌组织和血清中其诊断结直肠癌的AUC分别为0.845 7[95%CI（0.772 8，0.918 6），P<0.000 1]和0.868 3[95%CI（0.790 7，0.945 9），P<0.000 1]；在息肉患者血清中，hsa_circ_0078607诊断结直肠息肉的AUC为0.710 1 [95%CI（0.610 0，0.810 1）]。GO/KEGG富集分析结果表明，hsa_circ_0078607下游的miRNA可能参与RNA聚合酶Ⅱ启动子转录调控、蛋白K48-连锁泛素化、Wnt、Hippo及MAPK信号通路调控等多个生物过程。结论：Hsa_circ_0078607在结直肠癌细胞、组织和血清中呈高表达，其在结直肠癌组织中的表达水平与肿瘤位置、分化程度和远处转移有关联，提示其可作为结直肠癌潜在的分子诊断标志物；其还可能介导结直肠癌的发生发展过程，对发现结直肠癌潜在的治疗靶点有重要意义。

Advances in the Study of Antitumour Immunotherapy for Newcastle Disease Virus.

This article reviews the preclinical research, clinical application and development of Newcastle disease virus (NDV) in the field of cancer therapy. Based on the distinctive antitumour properties of NDV and its positive interaction with the patient's immune system, this biologic could be considered a major breakthrough in cancer treatment. On one hand, NDV infection creates an inflammatory environment in the tumour microenvironment, which can directly activate NK cells, monocytes, macrophages and dendritic cells and promote the recruitment of immune cells. On the other hand, NDV can induce the upregulation of immune checkpoint molecules, which may break immune tolerance and immune checkpoint blockade resistance. In fact, clinical data have shown that NDV combined with immune checkpoint blockade can effectively enhance the antitumour response, leading to the regression of local tumours and distant tumours when injected, and this effect is further enhanced by targeted manipulation and modification of the NDV genome. At present, recombinant NDV and recombinant NDV combined with immune checkpoint blockers have entered different stages of clinical trials. Based on these studies, further research on NDV is warranted.