Background: Tracheal, bronchial, and lung (TBL) cancer presents significant health challenges for individuals aged 70 and older. However, comprehensive insights into the epidemiological patterns of and risk factors for TBL cancer in this population remain limited. This study aimed to analyze the global, regional, and national burdens and trends of TBL cancer patients aged ≥ 70 years from 1990–2021. Methods: The incidence, mortality, and disability-adjusted life years (DALYs) for TBL cancer patients aged ≥ 70 years from 1990–2021 were obtained from the 2021 Global Burden of Disease study. Global trends were stratified age, sex, and sociodemographic index (SDI). Decomposition analysis identified the primary drivers of burden changes, and a global risk attribution analysis was conducted. The Bayesian Age‒Period‒Cohort (BAPC) model forecasted trends over the next 14 years. The analyses were performed with Joinpoint software and the R software. Results: From 1990–2021, the ASIRs, ASMRs, and ASDRs of TBL cancer among patients ≥ 70 years increase significantly, mainly due to aging and population growth. In the precision medicine era (2015–2021), these indicators for both sexes and males have declined, but the burden among females has increased. The burden varies across regions, with the incidence of TBL cancer increasing more severely in middle-SDI regions, East Asia, and western sub-Saharan Africa, whereas high-SDI regions have shown a decline after peaking. Although the DALY proportion of smoking decreased, it was still the main cause of TBL cancer. However, the burden of environmental particulate pollution has increased. The BAPC model predicted that in the future, the ASIR, ASMR, and ASDR for males and both sexes would decrease, whereas these indicators would either remain stable or increase among females. Conclusions: The burden of TBL cancer is increasing significantly among patients aged ≥ 70 years. Despite new hopes and approaches from precision medicine, environmental and behavioral factors still critically influence the TBL cancer burden. Future strategies could enhance subgroup-specific management and promote effective control of known risk factors.

The link between viruses and cancer has intrigued scientists for decades. Certain viruses have been shown to be vital in the development of various cancers by integrating viral DNA into the host genome and activating viral oncogenes. These viruses include the Human Papillomavirus (HPV), Hepatitis B and C Viruses (HBV and HCV), Epstein-Barr Virus (EBV), and Human T-Cell Leukemia Virus (HTLV-1), which are all linked to the development of a myriad of human cancers. Third-generation sequencing technologies have revolutionized our ability to study viral integration events at unprecedented resolution in recent years. They offer long sequencing capabilities along with the ability to map viral integration sites, assess host gene expression, and track clonal evolution in cancer cells. Recently, researchers have been exploring the application of Oxford Nanopore Technologies (ONT) nanopore sequencing and Pacific BioSciences (PacBio) single-molecule real-time (SMRT) sequencing in cancer research. As viral integration is crucial to the development of cancer via viruses, third-generation sequencing would provide a novel approach to studying the relationship interlinking viral oncogenes, viruses, and cancer. This review article explores the molecular mechanisms underlying viral oncogenesis, the role of viruses in cancer development, and the impact of third-generation sequencing on our understanding of viral integration into the human genome.

This review discusses the recent developments in copper-based nanomaterials that utilize copper-induced cell death, categorized by materials systems, while highlighting the limitations of current cuproptosis related copper-based nanomaterials.

Crizotinib (CRZ), one of anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs), has emerged as a frontline treatment for ALK-positive (ALK+) lung adenocarcinoma. However, the overexpression of P-glycoprotein (P-gp, a mitochondrial adenosine triphosphate (ATP)-dependent protein) in lung adenocarcinoma lesions causes multidrug resistance and limits the efficacy of CRZ treatment. Herein, a mitochondria-targeting nanosystem, zeolitic imidazolate framework-90@indocyanine green (ZIF-90@ICG), was fabricated to intervene in mitochondria and overcome drug resistance. Due to the zinc ion (Zn²⁺) interference of ZIF-90 and the photodynamic therapy (PDT) of ICG, this nanosystem is well suited for damaging mitochondrial functions, thus downregulating the intracellular ATP level and inhibiting P-gp expression. In addition, systematic bioinformatics analysis revealed the upregulation of CD44 in CRZ-resistant cells. Therefore, hyaluronic acid (HA, a critical target ligand of CD44) was further modified on the surface of ZIF-90@ICG for active targeting. Overall, this ZIF-90@ICG nanosystem synergistically increased the intracellular accumulation of CRZ and reversed CRZ resistance to enhance its anticancer effect, which provides guidance for nanomedicine design to accurately target tumours and induce mitochondrial damage and represents a viable regimen for improving the prognosis of patients with ALK-TKIs resistance. STATEMENT OF SIGNIFICANCE: The original aim of our research was to combat multidrug resistance (MDR) in highly aggressive and lethal lymphoma kinase-positive (ALK+) lung adenocarcinoma. For this purpose, a cascade-targeted system was designed to overcome MDR, integrating lung adenocarcinoma-targeted hyaluronic acid (HA), mitochondrion-targeted zeolitic imidazolate framework-90 (ZIF-90), the clinically approved drug crizotinib (CRZ), and the fluorescence imaging agent/photosensitizer indocyanine green (ICG). Moreover, using a "two birds with one stone" strategy, ion interference and oxidative stress induced by ZIF-90 and photodynamic therapy (PDT), respectively, disrupt mitochondrial homeostasis, thus downregulating adenosine triphosphate (ATP) levels, inhibiting MDR-relevant P-glycoprotein (P-gp) expression and suppressing tumour metastasis. Overall, this research represents an attempt to implement the concept of MDR reversal and realize the trade-offs between MDR and therapeutic effectiveness.

Lung cancer (LC) is one of the most incident malignancies and a leading cause of cancer mortality worldwide. Common tumorigenic drivers of LC mainly include genetic alterations of EGFR, ALK, KRAS, BRAF, ROS1, and MET. Small inhibitory molecules and antibodies selectively targeting these alterations or/and their downstream signaling pathways have been approved for treatment of LC. Unfortunately, following initial positive responses to these targeted therapies, a large number of patients show dismal prognosis due to the occurrence of resistance mechanisms, such as novel mutations of these genes and activation of alternative signaling pathways. Over the past decade, it has become clear that there is no possible cure for LC unless potent antitumor immune responses are induced by therapeutic intervention. Immunogenic cell death (ICD) is a newly emerged concept, a form of regulated cell death that is sufficient to activate adaptive immune responses against tumor cells. It transforms dying cancer cells into a therapeutic vaccine and stimulates long-lasting protective antitumor immunity. In this review, we discuss the key targetable genetic aberrations and the underlying mechanism of ICD in LC. Various agents inducing ICD are summarized and the possibility of harnessing ICD in LC immunotherapy is further explored.

Respiratory diseases pose a severe threat to global health, with notable limitations in current diagnosis and treatment, such as insufficient sensitivity of diagnostic tools and a lack of effective targeted therapies. Due to their highly efficient information transmission capabilities and excellent safety profile, exosomes carrying non-coding RNA, particularly microRNA (miRNA), are increasingly attracting attention. Compared with free miRNAs, exosomes can protect miRNAs from nuclease degradation, prolong their circulation time in the body, thereby improving the stability and bioavailability of miRNAs. At the same time, they can also address the major bottleneck in the clinical application of miRNAs, including low in vivo delivery efficiency, poor stability, lack of targeting specificity, and off-target effects. Increasing evidence indicate that miRNAs play a significant role in respiratory diseases, including targeting multiple signaling pathways, regulating inflammation and oxidative stress, influencing tumor growth and apoptosis, and participating in tissue damage and repair, thus holding promising prospects for diagnosis and treatment in respiratory diseases. MSC-derived exosomes exhibit low tumorigenic risk because they originate from adult stem cells with limited differentiation ability, have low immunogenicity, and do not highly express major histocompatibility complex class II (MHC-II) molecules, making them suitable for allogeneic use. To enhance the therapeutic efficacy and specificity of exosomes in respiratory diseases, engineering modifications of MSC-exosomes (MSC-exos) are crucial. Current methods for engineering MSC-exos primarily include cargo loading and surface modification to improve therapeutic efficacy and targeting specificity. Through these engineering methods, more precise miRNA delivery can be achieved, reducing the side effects of traditional treatments and improving treatment efficacy. Although MSC-exos demonstrate significant potential in treating respiratory diseases, their clinical translation is hindered by critical hurdles, including individual differences in therapeutic efficacy, insufficient miRNA targeting specificity, challenges in large-scale production, and potential immunogenicity risks. To accelerate clinical application, future research should prioritize optimizing engineered targeting strategies (eg, precision surface modification), enhancing large-scale preparation efficiency of functional MSC-exos, and validating their long-term safety and efficacy in multi-center studies. At present, the good manufacturing practice (GMP) production process of MSC-exos has been established. Early clinical trials (Phase I/II) have shown its potential in respiratory diseases such as pulmonary fibrosis without serious adverse reactions. However, it has not yet been approved for clinical transformation and still faces challenges such as large-scale targeting and safety. Overall, MSC-exos carrying miRNAs show great promise in the treatment of respiratory diseases, but their true clinical application still requires more systematic research and validation.