Treatment Of Lung Cancer Research Articles

Progress and challenges in clinical diagnosis and treatment of co-existent lung cancer and pulmonary tuberculosis

Lung cancer is the leading cause of malignancy-related morbidity and mortality in China and worldwide, posing a significant threat to human well-being. Tuberculosis (TB) is the second leading cause of death from a single infectious source, after COVID-19 infection, and represents a public health crisis. Recent research has shown that TB is an independent risk factor for lung cancer, while patients with lung cancer may also be at increased risk of TB. The occurrence of TB poses to a challenge to the implementation of the anti-cancer therapy in lung cancer. Early identification and appropriate treatment are essential for the prognosis improvement. Therefore, in this review, we aimed to highlight the research advances and challenges in the diagnosis and treatment of lung cancer and TB co-existence, with the further aim of providing new insights into the clinical management of patients and future research.

Clinical diagnosis and treatment of lung cancer combined with interstitial lung disease

Lung cancer and interstitial lung disease have similar risk factors and pathogenesis. The incidence of lung cancer associated with interstitial lung disease is increasing, and the problem of comorbidity has gradually attracted attention. Early diagnosis of lung cancer associated with interstitial lung disease is difficult, there are many factors influencing treatment, and the prognosis is poor. Interstitial lung disease affects the treatment options for lung cancer in comorbid patients, and lung cancer treatment will increase the risk of acute exacerbation of interstitial lung disease in comorbid patients. For patients with early-stage lung cancer complicated with interstitial lung disease who have surgical indications, the surgical method and extend of resection should be determined on the basis of MDT according to tumor stage and lung function. For patients with early-stage lung cancer combined with interstitial lung disease who are not suitable for surgery, the benefits and risks of complications of the radiotherapy should be weighed, and the appropriate radiotherapy regimen and dose should be selected. Chemotherapy is an effective treatment for patients with advanced lung cancer complicated with interstitial lung disease. Some chemotherapy regimens cause acute progression of interstitial lung disease, and the choice of chemotherapy regimen is particularly important. For lung cancer patients with interstitial lung disease who are positive for driver gene mutations, targeted drugs with low pulmonary toxicity should be selected. Patients with lung cancer combined with interstitial lung disease may benefit from immunotherapy, but the risk of immune-related pneumonia is increased. The occurrence of adverse reactions should be closely monitored during immunotherapy. In the future, more prospective clinical trials are needed to formulate reasonable and effective treatment regimens for lung cancer combined with interstitial lung disease to achieve a better prognosis.

Brief analysis of diagnosis and treatment of lung cancer complicated by chronic obstructive pulmonary disease

Lung cancer and chronic obstructive pulmonary disease share common risk factors and the same pathophysiological mechanisms, which are a common comorbidities and interact with each other. At present, there is no universal standard for diagnosis and treatments, and these patients have a poor prognosis. Pulmonary function detection and regular low-dose spiral CT can improve the diagnosis rate of the comorbid disease. The principle of "co-morbidities, co-treatment of cancer and lung disease" should be fully considered in the process of diagnosis and treatment.

The current state and trends of immunotherapy research in lung cancer: a review and bibliometric analysis

In recent years, the integration of immunotherapy in the treatment of lung cancer has marked a significant evolution in the field. This is evidenced by the surge in the volume of scientific publications, reflecting rapid advances over time. This paper presents a bibliometric analysis of lung cancer and immunotherapy research from January 2012 to December 2022, drawing on the Web of Science literature database and using the citexs data analysis platform to examine the shifts in topic hotspots over the decade. A total of 8,722 publications were retrieved, with annual publication numbers soaring from 79 in 2012 to 2,112 in 2021. The most prolific country in terms of publication volume was China (n = 3,363, 38.56%), with The University of Texas MD Anderson Cancer Center making the most significant institutional contribution (n = 156, 1.79%). Notably, the most productive authors in this domain were Benjamin Besse and Marina Chiara Garassino, who have collectively published 35 articles to date. Predominant research themes include PD1/PDL1, clinical trials, pembrolizumab, nivolumab, and immune checkpoint inhibitors. Moreover, this paper visualizes the analysis of journals, keywords, key genes and targets, and associated diseases, aiming to provide a systematic review and a forward-looking perspective on research in lung cancer and immunotherapy. By exploring current research dynamics and hotspots and identifying areas for improvement, this study seeks to provide valuable insights for future investigations in this burgeoning field.

In Brief: A New Non-Small Cell Lung Cancer Indication for Osimertinib (Tagrisso)

The oral kinase inhibitor osimertinib (Tagrisso – AstraZeneca), which has been available for years for treatment of non-small cell lung cancer (NSCLC) in adults with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, has now been approved for treatment of unresectable stage III EGFR-mutated NSCLC.1 About 20-30% of patients with NSCLC have locally advanced stage III NSCLC, and 60-90% of these patients have unresectable disease. Osimertinib is the first targeted therapy to be approved for the new indication.

Cost-effectiveness analysis of lorlatinib and crizotinib in the first-line treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer

ABSTRACT Objectives To assess the economic value of lorlatinib and crizotinib in the first-line treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer at medical insurance negotiation prices from the viewpoint of China’s health system. Methods Based on data from the phase III clinical trial, a three-state partitioned survival model was established. In combination with parameters such as treatment costs, utility values, incidence of adverse reactions, and discount rates, the total incremental cost-effectiveness ratio (ICER) was simulated. Results The results of the fundamental analysis indicated that the patients in the lorlatinib group expended 709,671 yuan more than did the patients in the crizotinib group did but gained 3.09 quality-adjusted life years (QALYs). The ICER value was 229,782.6 yuan/QALY, which was lower than three times the per capita gross domestic product (GDP) of China. Conclusions Compared with crizotinib, lorlatinib may be a cost-effective first-line treatment choice for advanced ALK-positive NSCLC in China.

Dual targeting and bioresponsive nano-PROTAC induced precise and effective lung cancer therapy

Epigenetic regulation has emerged as a promising therapeutic strategy for lung cancer treatment, which can facilitate the antitumor responses by modulating epigenetic dysregulation of target proteins in lung cancer. The proteolysis-targeting chimera (PROTAC) reagent, dBET6 shows effective inhibition of bromodomain-containing protein 4 (BRD4) that exerts antitumor efficacy by degrading BRD4 via the ubiquitin-proteasome system. Nevertheless, the low tissue specificity and bioavailability impede its therapeutic effects and clinical translation on lung cancer treatment. Herein, we developed a type of dual targeting and bioresponsive nano-PROTAC (c R GD/L LC membrane/D S-P LGA/d B ET6, named RLDPB), which was constructed by using the pH and glutathione (GSH)-responsive polymer, disulfide bond-linked poly(lactic-co-glycolic acid) (PLGA-S-S-PLGA, DS-PLGA) to load the PROTAC agent dBET6, and further camouflaged with the homotypic LLC cell membranes, followed by the conjugation with cRGD ligand to the surface of the nanoparticles. Notably, RLDPB showed enhanced celluar uptake by lung cancer cells in vitro and accumulation in the tumors via the dual targeting structure including cRGD and LLC membrane. The pH/GSH responsiveness improved the release of dBET6 from the DS-PLGA-based nanoparticles within the cells. RLDPB was demonstrated to facilitate tumor regression by inducing the apoptosis of lung cancer cells with the degradation of BRD4. Thus, RLDPB can be considered a powerful tool to suppress lung cancer, which opens a new avenue to treat lung cancer by PROTAC.Graphical abstract

Hesperidin’s role in the treatment of lung cancer: In-silico and In-vitro findings

Hesperidin’s role in the treatment of lung cancer: In-silico and In-vitro findings

Cell components of tumor microenvironment in lung adenocarcinoma: Promising targets for small-molecule compounds

Abstract Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%, mainly including lung adenocarcinoma (LUAD). Tumor microenvironment (TME) has become a new research focus in the treatment of lung cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. The various cellular components exert a different role in apoptosis, metastasis, or proliferation of lung cancer cells through different pathways, thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods. This review summarizes the research progress on different cellular components with cell–cell interactions in the TME of LUAD, along with their corresponding drug candidates, suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.

A causal association between chemokines and the risk of lung cancer: a univariate and multivariate mendelian randomization study

BackgroundObservational studies and experimental evidence have shown that chemokines play important roles in lung cancer development, progression, and treatment. However, few studies have examined the causal association between them.MethodsSummary data of chemokines and lung cancer were obtained from genome-wide association studies. Mendelian randomization (MR) analyses were performed by five methods, Inverse variance weighted (IVW), Weighted median estimation, MR-Egger, Simple mode and Weighted, with IVW as the primary analysis method. Sensitivity analysis was used to assess the reliability of the MR results. Multivariate Mendelian randomization studies were used to infer whether causality was influenced by potential mediators. The expression levels of CCL21 were analyzed by quantitative real-time PCR.ResultsWe found that CCL21 was negatively associated with lung adenocarcinoma risk. CCL25 was positively associated with lung squamous cell carcinoma risk. CCL5 was negatively associated with small cell lung cancer risk. CCL21, CCL24, CCL27, and CCL28 was positively associated with small cell lung cancer risk. After multivariate Mendelian randomization adjustment for smoking behavior, it was found that the effect of CCL25 on lung squamous cell cancer disappeared, and the effect of CCL21 on small cell lung cancer was quite opposite to the univariate. The receiver operating characteristic curve indicated that chemokines had high accuracy in the diagnosis of lung cancer. CCL21 expression levels showed large differences in lung adenocarcinoma cells.ConclusionThese results highlighted the causal effects of chemokines on lung cancer and suggested a mediating role of smoking behavior in the association between chemokines and lung cancer.

Update on Practical Management of Early-Stage Non-Small Cell Lung Cancer (NSCLC): A Report from the Ontario Forum

Therapeutic strategies for early-stage non-small cell lung cancer (NSCLC) are advancing, with immune checkpoint inhibitors (ICIs) and targeted therapies making their way into neoadjuvant and adjuvant settings. With recent advances, there was a need for multidisciplinary lung cancer healthcare providers from across Ontario to convene and review recent data from practical and implementation standpoints. The focus was on the following questions: (1) To what extent do patient (e.g., history of smoking) and disease (e.g., histology, tumor burden, nodal involvement) characteristics influence treatment approaches? (2) What are the surgical considerations in early-stage NSCLC? (3) What is the role of radiation therapy in the context of recent evidence? (4) What is the impact of biomarker testing on treatment planning? Ongoing challenges, treatment gaps, outstanding questions, and controversies with the data were assessed through a pre-meeting survey, interactive cases, and polling questions. By reviewing practice patterns across Ontario cancer centers in the context of evolving clinical data, Health Canada indications, and provincial (Cancer Care Ontario [CCO]) funding approvals, physicians treating lung cancer voiced their opinions on how new approaches should be integrated into provincial treatment algorithms. This report summarizes the forum outcomes, including pre-meeting survey and polling question results, as well as agreements on treatment approaches based on specific patient scenarios.

Efficacy and Safety of a Therapy Combining Sintilimab and Chemotherapy With Cryoablation in the First-Line Treatment of Advanced Nonsquamous Non–Small Cell Lung Cancer: Protocol for a Phase II, Pilot, Single-Arm, Single-Center Study

Background Immunotherapy has significantly advanced lung cancer treatment, particularly in nonsquamous non–small cell lung cancer (NSCLC), with overall response rates between 50% and 60%. However, about 30% of patients only achieve a stable disease state. Cryoablation has shown potential to enhance immunotherapy by modifying the tumor’s immune microenvironment through the release of antigens and immune factors. Addressing how to boost the immune response in these patients is critical. Objective This study aims to investigate the efficacy and safety of immunochemotherapy in combination with cryoablation as a first-line treatment for advanced NSCLC. Methods This is a phase II, pilot, open-label, single arm, single center, interventional study. Patients with stage IIIB to IIIC or IV NSCLC with T staging ranging from T1 to T2b will receive sintilimab (200 mg/m2 every 3 weeks) and chemotherapy. After 2 cycles, the feasibility of cryoablation will be considered for those with stable disease by a multidisciplinary team. Cryoablation with 3 freeze-thaw cycles will be performed for the main lesion. The third cycle of systemic therapy will begin 7 (SD 3) days after cryoablation. A total of 20 patients will be enrolled. Treatment will continue until the disease progresses, there is unacceptable toxicity, a participant withdraws consent, other discontinuation criteria are met, or the study reaches completion. The primary objective is to assess progression-free survival (PFS). The secondary objective is to assess efficacy through duration of response, disease control rate, overall survival (OS), and the safety profile. The exploratory objective is to investigate and compare immune factor changes after 2 cycles of immunochemotherapy and at 1, 3, and 7 days after cryoablation. Survival time will be estimated using the Kaplan-Meier method to calculate median PFS and OS. Any adverse events that occur during the trial will be promptly recorded. Results The project was funded in 2024, and enrollment will be completed in 2025. The first results are expected to be submitted for publication in 2027. Conclusions This study will provide evidence for the efficacy and safety of the combination of immunochemotherapy and cryoablation as a first-line treatment for advanced NSCLC. Although it has a limited sample size, the findings of this study will be used in the future to inform the design of a fully powered, 2-arm, larger-scale study. Trial Registration ClinicalTrials.gov NCT06483009; https://clinicaltrials.gov/study/NCT06483009 International Registered Report Identifier (IRRID) PRR1-10.2196/64950

Design and Optimization of Quinazoline Derivatives as Potent EGFR Inhibitors for Lung Cancer Treatment: A Comprehensive QSAR, ADMET, and Molecular Modeling Investigation

Design and Optimization of Quinazoline Derivatives as Potent EGFR Inhibitors for Lung Cancer Treatment: A Comprehensive QSAR, ADMET, and Molecular Modeling Investigation

SYNERGISTIC EFFECT LUNG CANCER THERAPY: CO-DELIVERY OF QUERCETIN AND CISPLATIN VIA EUDRAGIT L-100 NANOPARTICLES IN VITRO

Objective: This study aims to investigate the potential of Eudragit L-100 nanoparticles for the co-delivery of quercetin and cisplatin to lung cancer cells, seeking to exploit the synergistic effects of the two drugs while overcoming their individual limitations. Methods: We investigate the synergistic effect of co-delivering quercetin and cisplatin using Eudragit L-100 nanoparticles for lung cancer therapy. The nanoparticles were synthesized using the nanoprecipitation method, where Eudragit L-100 was dissolved in an organic solvent, followed by the incorporation of quercetin and cisplatin. The resultant nanoparticles were characterized for size, zeta potential, drug loading efficiency, and morphology using techniques such as Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM). Results: The co-loaded Quercetin-Cisplatin Nanoparticles (Qu-Cis)-NPs formulation had a mean particle size of 475±4.77 nm. Polydispersion index of 0.266±0.093 and zeta potential was-24.03±0.89 mV. The in vitro cytotoxicity was assessed using normal cell and lung cancer cell lines in vitro studies showed that the developed nanoparticles significantly increased cancer cell mortality compared to individual drug treatments. The combination (Qu-Cis)-NPs showed more cytotoxicity on the Non-Small Lung Cancer Cell Line (NCI-H460) cancer cell line after 48 h of incubation compared to Qu loaded-NPs and Cis loaded-NPs, particularly at a concentration of 1 mg/ml. The combination showed no cytotoxicity effect on normal Human Lung fibroblast cell Lines (CCD-19 lu) cells at all concentrations after 24 h, but showed cytotoxicity effects at concentrations (0.125, 0.25, 0.5, and 1.0) mg/ml after 48 h. Conclusion: The Eudragit L-100 nanoparticle system for co-delivering quercetin and cisplatin showed a promising synergistic effect in lung cancer treatment. It effectively addresses the solubility and toxicity issues of both drugs, offering a potentially more effective treatment option that merits further clinical investigation.

The clinical pathway in China county for lung cancer diagnosis and treatment (2024 edition)

Standardizing the diagnosis and treatment of lung cancer is a key measure to improve the survival rate of lung cancer patients and reduce the mortality rate. However, county hospitals generally face the problem of inaccessibility to advanced diagnostic and treatment technologies. Therefore, when developing quality control standards and clinical diagnosis and treatment specifications, it is necessary to combine the actual situation of county hospitals and formulate specific recommendations. The recommendations of treatment measures also need to consider the approval status of indications and whether it is included in the National Reimbursement Drug List (NRDL), to ensure the access to medicines. To address the above issues, based on the existing guidelines at home and abroad and the clinical work characteristics of county hospitals, the " the clinical pathway in China county for lung cancer diagnosis and treatment (2024 edition)" has been updated on the basis of the first edition. This pathway elaborated on the imaging diagnosis, pathological diagnosis, molecular testing, precision medicine, and developed different diagnosis and treatment processes for different types of lung cancer patients. Consistent with the first pathway, this update still divides the recommendations for diagnosis and treatment of clinical scenarios into basic strategies and optional strategies for elaboration. The basic strategies are the standards that county hospitals must meet, while the optional strategies provide more choices for hospitals, which are convenient for county doctors to put into clinical practice. All the recommended diagnostic and treatment plans strictly refer to existing guidelines and consensus. Compared to the first edition, based on the latest high-level evidence-based medicine and the approval status of indications, the pathway has updated the diagnosis and treatment recommendations for lung cancer under different pathological types, TNM classification, and molecular classification in basic and optional strategies.

Tri-Responsive Drug Delivery System for Lung Cancer Treatment: Enhanced Photothermal Conversion and Targeted Apoptosis in H1299 Cells

Tri-Responsive Drug Delivery System for Lung Cancer Treatment: Enhanced Photothermal Conversion and Targeted Apoptosis in H1299 Cells

KRAS inhibitors in drug resistance and potential for combination therapy.

Kirsten Rat Sarcoma (KRAS) is a potent target for cancer therapy because it acts as a signaling hub, engaging in various signaling pathways and regulating a number of cellular functions like cell differentiation, proliferation, and survival. Recently, an emergency approval from the US-FDA has been issued for KRASG12C inhibitors (sotorasib and adagrasib) for metastatic lung cancer treatment. However, clinical studies on covalent KRASG12C inhibitors have rapidly confronted resistance in patients. Many methods are being assessed to overcome this resistance, along with various combinatorial clinical studies that are in process. Moreover, because KRASG12D and KRASG12V are more common than KRASG12C, focus must be placed on the therapeutic strategies for this type of patient, along with sustained efforts in research on these targets. In the present review, we try to focus on various strategies to overcome rapid resistance through the use of combinational treatments to improve the activity of KRASG12C inhibitors.

Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer.

Immune checkpoint inhibitors (ICIs) are drugs that inhibit immune checkpoint (ICP) molecules to restore the antitumor activity of immune cells and eliminate tumor cells. Due to the limitations and certain side effects of current ICIs, such as programmed death protein-1, programmed cell death-ligand 1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) antibodies, there is an urgent need to find new drugs with ICP inhibitory effects. In this study, a network-based computational framework called multi-network algorithm-driven drug repositioning targeting ICP (Mnet-DRI) is developed to accurately repurpose novel ICIs from ≈3000 Food and Drug Administration-approved or investigational drugs. By applying Mnet-DRI to PD-L1, maprotiline (MAP), an antidepressant drug is repurposed, as a potential PD-L1 modifier for colorectal and lung cancers. Experimental validation revealed that MAP reduced PD-L1 expression by targeting E3 ubiquitin ligase speckle-type zinc finger structural protein (SPOP), and the combination of MAP and anti-CTLA4 in vivo significantly enhanced the antitumor effect, providing a new alternative for the clinical treatment of colorectal and lung cancer.

Artificial Intelligence in Lung Cancer Detection: Clinical and Economic Assessment of Retrospective CT Analysis Two Years Post-COVID-19 Pandemic

BACKGROUND: The use of chest computed tomography (CT) scans in Krasnoyarsk Krai, Russia, has increased since 2020, during the COVID-19 pandemic. This period also saw a 5.2% decrease in lung cancer (LC) incidence. The potential for missed LC cases has led to the investigation of new diagnostic methods, including the use of artificial intelligence (AI) for analyzing retrospective data. AIM: The study aimed to evaluate the effectiveness of an AI algorithm in identifying patients at high risk for LC using chest CT data from the COVID-19 pandemic. METHODS: A retrospective analysis was conducted on chest CTs from patients diagnosed with COVID-19 in the Krasnoyarsk region, using scans from November 1, 2020, to February 28, 2021. The AI algorithm "Chest-IRA" was applied to detect pulmonary nodules larger than 100 mm³. Radiologists classified the nodules detected by AI into three categories based on LC probability. The economic assessment of the AI algorithm included salary costs and potential savings from early LC treatment. RESULTS: Out of 10,500 CTs, the AI algorithm found nodules in 484 cases. Of these, 192 were highly likely to have LC, 103 showed no signs, and 60 were inconclusive. 112 patients with high or intermediate risk did not seek treatment. The AI confirmed lung cancer in 100 cases, 28.2% of those detected. Early-stage LC was found in 35% of cases, while 65% were at later stages. AI could save about 25.04 months of radiologist work, costing 2.43 million RUB. Early detection savings are estimated at 10.6 to 12.5 million RUB per 10,500 CTs, with a five-year economic impact of 259.4 to 305.1 million RUB. CONCLUSION: AI has proven effective in identifying pulmonary nodules amidst COVID-19, highlighting its potential to improve early detection and diagnostic accuracy, leading to earlier and more precise treatments.

Real-world evidence for pembrolizumab in non-small cell lung cancer: a nationwide cohort study.

Based on favourable results from clinical trials, immune checkpoint inhibitors (ICI) have become the standard first line (1 L) systemic anticancer treatment (SACT) for advanced stage non-small cell lung cancer (NSCLC) without targetable mutations. We evaluate whether these results are generalizable to everyday clinical practice and compare overall survival (OS) of patients treated with ICI to a historical cohort of patients treated with chemotherapy and results from clinical trials. Our study comprised all advanced NSCLC patients initiating SACT in 2012-21 in Norway. Clinical characteristics and treatment information was retrieved from Norwegian Health Registries. Survival for all 8416 advanced NSCLC patients treated with SACT increased concurrently with the gradual implementation of ICIs. Median OS of patients treated with 1 L pembrolizumab after 2017 was better (mono-/combination therapy: 13.8/12.8 months) than for patients treated with chemotherapy before 2017 (8.0 months). Although median OS for patients treated with pembrolizumab was lower in clinical practice than clinical trials (Keynote-024/189: 26.3/22.0 months), the survival benefit relative to chemotherapy was similar. Our nationwide study demonstrated a survival benefit over conventional chemotherapy of a similar magnitude as observed in clinical trials and confirms the effectiveness of pembrolizumab in routine clinical practice.