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Relevant Articles About Research and Clinical Trials in Lung Cancer

RELATED :SCLC (Small Cell Lung Cancer):NSCLC (Non-Small Cell Lung Cancer)

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Human stomach with endoscope and close-up of Helicobacter pylori bacterium
Gastrointestinal Cancer

Efficacy and Safety Of NAIT in GEJC

KEY TAKEAWAYS The study aimed to investigate the efficacy and safety of NAIT in patients with GEJC. Researchers noticed the efficacy of NAIT in resectable GEJC alongside an acceptable toxicity profile; further investigation is ongoing. In recent years, neoadjuvant...

May 16, 2024

Abemaciclib and Fulvestrant for Breast Cancer
Breast Cancer

Overlapping Ages: Pregnancy & Breast Cancer Awareness

KEY TAKEAWAYS The study aimed to compare populations with differing childbirth ages to assess breast cancer and childbearing age overlap. The study emphasized increased awareness for women to make informed choices about delayed childbearing and cancer prevention....

May 16, 2024

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Lung Cancer Decision Aid: Innovative Search & Expert Engagement

KEY TAKEAWAYS

  • The study aimed to examine the implementation of the decision tool for lung cancer treatment consultations within the I3LUNG project.
  • The study concluded to enhance lung cancer decision aids by exploring diverse outcomes, consulting experts, and developing patient-focused guidelines.

Lung cancer remains one of the deadliest diagnoses globally, necessitating a range of available treatments and modalities typically discussed during patient-doctor consultations. Integrating decision tools into medical consultations is crucial to aid patients in decision-making and healthcare management. Research indicates that decision tools effectively support patients with lung cancer in making informed decisions and managing their health during consultations.

Valeria Sebri and the team aimed to systematically review the implementation of decision tools to facilitate medical consultations regarding oncological treatments for patients with lung cancer in the I3LUNG project.

Researchers conducted a systematic review adhering to the PRISMA guidelines. They performed an electronic computer-based search across three databases: Embase, PubMed, and Scopus. About 10 articles meeting the inclusion criteria were selected. These articles specifically addressed decision tools within the context of oncology, focusing on patients with lung cancer.

The discussion emphasizes the promising findings regarding the beneficial impact of decision aids in medical consultations concerning oncological treatments, particularly concerning anxiety, decision-making, and patient knowledge. However, no single predominant decision aid tool was identified. Selecting a more recent timeframe to include articles could provide insights into the current landscape of available decision-aid tools.

The study concluded that future review efforts may benefit from alternative search strategies to explore additional lung cancer-specific outcomes during medical consultations for treatment decisions and the implementation of decision aid tools. Engaging with experts in oncology, patient decision-making, or health communication could provide valuable insights and recommendations for relevant literature or research directions that may not be readily accessible through traditional search methods. The development of guidelines for future research aims to promote decision aids focused on meeting patients’ needs.

Funding was provided by the European Union’s Horizon 2020 caLL topic “HORIZON-HLTH-2021-CARE-05-02—Data-driven decision-support tools for better health care delivery and policy-making with a focus on cancer.”

Source: https://pubmed.ncbi.nlm.nih.gov/38741546/

Sebri V, Marzorati C, Dorangricchia P, et al. (2024). “The impact of decision tools during oncological consultation with lung cancer patients: A systematic review within the I3LUNG project.” Cancer Med. 2024 May;13(9):e7159. doi: 10.1002/cam4.7159. PMID: 38741546.

Promising Lung Cancer Therapy: HCTMPPK as MELK Inhibitor

KEY TAKEAWAYS

  • The study aimed to evaluate the role of a novel chalcone derivative of tetramethylpyrazine, HCTMPPK, in lung adenocarcinoma.
  • The study’s findings suggested that HCTMPPK could be a promising candidate for lung cancer therapy by acting as a potential MELK inhibitor.

Lung adenocarcinoma stands as one of the primary causes of cancer-related deaths globally. Various anti-inflammatory herbs, such as tetramethylpyrazine, have demonstrated potential in combating tumors.

Yan Ma and the team aimed to examine the function of a new chalcone derivative of tetramethylpyrazine, termed HCTMPPK, in lung adenocarcinoma.

The study investigated the effects of HCTMPPK on cell proliferation, apoptosis, and invasion through in-vitro assays, including CCK-8, colony formation, flow cytometry, transwell, and wound-healing assays. The therapeutic potential of HCTMPPK was assessed in vivo. To identify the target molecules of HCTMPPK, researchers employed a network pharmacology approach and conducted molecular docking studies, followed by experiments to confirm these candidate molecules.

The results revealed that HCTMPPK effectively suppressed the proliferative activity and migration of A549 cells and enhanced apoptosis in a concentration-dependent manner. In vivo experiments showed significant inhibition of tumor growth by HCTMPPK. Mechanistically, HCTMPPK down-regulated Bcl-2 and MMP-9 while up-regulating Bax and cleaved-caspase-3. Subsequently, 601 overlapping DEGs were identified from LUAD patients in TCGA and GEO databases. Fifteen hub genes were then identified through the PPI network and CytoHubba analysis. Finally, molecular docking studies and validation experiments confirmed MELK as the targeted site of HCTMPPK.

The study’s findings suggested that HCTMPPK shows promise as a potential MELK inhibitor and could emerge as a promising therapy candidate for lung cancer.

Funding was provided by the Open found project of NMPA Key Laboratory for Quality Research and Evaluation of Traditional Marine Chinese Medicine, Traditional Chinese Medicine Science and Technology Project of Qingdao Municipal Health Commission, Shinan District Science and Technology Plan Project, and Zaozhuang Medicine and Health Science and Technology Development Program Project.

Source: https://pubmed.ncbi.nlm.nih.gov/38737331/

Ma Y, Cui Q, Zhu W, et al. (2024). “A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK.” Drug Des Devel Ther. 2024 May 7;18:1531-1546. doi: 10.2147/DDDT.S449139. PMID: 38737331; PMCID: PMC11088378.

STK11 Mutation Correlates With Poor Prognosis in NSCLC

KEY TAKEAWAYS

  • The study aimed to examine the impact of overexpressed and mutated STK11 on NSCLC survival, exploring IRGs involvement in mutations.
  • The study concluded that low STK11 protein expression and its mutation correlate with poor NSCLC prognosis, potentially altering IRGs.

Mutations in the STK11 (STK11Mut) gene could negatively affect survival in patients with Non-small Cell Lung Cancer (NSCLC), but their connection to immune-related genes (IRGs) remains unclear.

Jianqing Zheng and the team aimed to determine the influence of overexpressed and mutated STK11 on survival in NSCLC and to investigate the involvement of IRGs in STK11 mutations.

The study included 188 patients with NSCLC who had intact formalin-fixed paraffin-embedded (FFPE) tissue to detect STK11 protein expression. After immunohistochemical detection of STK11 protein, patients were categorized into a high STK11 expression group (STK11High) and a low STK11 expression group (STK11Low). Kaplan-Meier survival analysis and COX proportional hazards model compared these groups’ overall survival (OS) and progression-free survival (PFS).

Additionally, mutation data from the TCGA database categorized the NSCLC population into STK11 Mutated (STK11Mut) and wild-type (STK11Wt) subgroups, with OS differences between them compared. Bioinformatics analysis compared IRG expression differences between STK11Mut and STK11Wt populations.

The results revealed that the median follow-up time for the real-life cohort was 51.0 months (range 3.0 – 120.0 months). By the end of follow-up, 64.36% (121/188) of patients experienced recurrence or metastasis, while 64.89% (122/188) succumbed to cancer-related death. High expression of STK11 emerged as a significant protective factor for NSCLC patients, both in terms of PFS [HR=0.42, 95% CI= (0.29-0.61), P<0.001] and OS [HR=0.36, 95% CI= (0.25, 0.53), P<0.001], consistent with findings in TCGA cohorts [HR=0.76, 95%CI= (0.65, 0.88), P<0.001 HR=0.76, 95%CI= (0.65, 0.88), P<0.001].

In the TCGA cohort, STK11 mutation emerged as a significant risk factor for NSCLC in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) histology in terms of OS [HR=6.81, 95%CI= (2.16, 21.53), P<0.001; HR=1.50, 95%CI= (1.00, 2.26), P=0.051, respectively]. Additionally, 7 IRGs—CALCA, BMP6, S100P, THPO, CGA, PCSK1, and MUC5AC—were significantly overexpressed in STK11-mutated NSCLC in both LUSC and LUAD histology.

The study concluded that in NSCLC, low protein-level expression of STK11 and the presence of STK11 mutation were linked with poor prognosis. Mutated STK11 likely alters the expression profiling of IRGs.

Research was funded by the Fujian Research and Training Grants, Joint Funds for the Innovation of Science and Technology, Fujian Province, Fujian Provincial Natural and Scientific Foundation, and the Fujian Provincial Clinical Research Center for Cancer Radiotherapy and Immunotherapy, Science and Technology projects of Quanzhou city, Fujian Provincial Health Technology Project, and Fujian Provincial Academic and Research Program for Young and Middle-age Teachers.

Source: https://pubmed.ncbi.nlm.nih.gov/38736875/

Zheng J, Deng Y, Huang B, et al. (2024). “Prognostic implications of STK11 with different mutation status and its relationship with tumor-infiltrating immune cells in non-small cell lung cancer.” Front Immunol. 2024 Apr 26;15:1387896. doi: 10.3389/fimmu.2024.1387896. PMID: 38736875; PMCID: PMC11082287.

TAN Dynamics: NSCLC Treatment & TME Insights

TAN Dynamics: NSCLC Treatment & TME Insights

KEY TAKEAWAYS

  • The study aimed to explore neutrophil heterogeneity in patients with NSCLC.
  • The study concluded TAN dynamics enhance NSCLC treatment understanding, aiding TME comprehension and advancement.

In the realm of lung cancer, a highly perilous malignant tumor with severe health implications, neutrophils have garnered increasing interest.

Yunzhen Wang and the team aimed to examine the diversity of neutrophils in non-small cell lung cancer (NSCLC).

The study analyzed single-cell RNA sequencing data of tumor-associated neutrophils (TANs) and polymorphonuclear neutrophils from the Gene Expression Omnibus database. Additionally, they conducted analyses on cell-cell communication, differentiation trajectories, and transcription factors.

The study of neutrophils showed a close association with macrophages. They identified 4 major types of TANs. These included a transitional subcluster (TAN-0) migrating from blood to the tumor microenvironment (TME), an inflammatory subcluster (TAN-1), a subpopulation with a distinctive transcriptional signature (TAN-2), and a final differentiation state promoting tumor formation (TAN-3). TAN-3 exhibited notably increased glycolytic activity. Additionally, the analysis of transcription factors revealed distinct regulons specific to each TAN cluster.

The study concluded that the dynamic characteristics of TANs are expected to enhance understanding of the TME and advance NSCLC treatment.

No funding-related information was available.

Source: https://pubmed.ncbi.nlm.nih.gov/38735760/

Wang Y, Zhu Z, Luo R, et al. (2024). “Single-cell transcriptome analysis reveals heterogeneity of neutrophils in non-small cell lung cancer.” J Gene Med. 2024 May;26(5):e3690. doi: 10.1002/jgm.3690. PMID: 38735760.

High ALI Reduces Stroke Mortality: Prognosis

KEY TAKEAWAYS

  • The study aimed to investigate the relationship between ALI and the prognosis of stroke patients.
  • Researchers noticed a reverse J-shaped non-linear link between ALI and all-cause mortality, underscoring the need to control ALI within a suitable range for better stroke prognosis.

Stroke was a major global public health challenge, and its prognosis was remarkably associated with inflammation levels and nutritional status. The advanced lung cancer inflammation index (ALI) was a comprehensive indicator that combined inflammation and nutritional status. The relationship between ALI and the prognosis of stroke patients was not yet known.

Xiaokun Chen and the team aimed to assess the utility of ALI in predicting outcomes for stroke patients.

They performed an inclusive analysis utilizing cohort data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. The association between ALI and all-cause and cardiovascular disease (CVD) mortality in stroke patients was estimated using a multivariable adjusted Cox model. Their non-linear relationship was analyzed by restricted cubic spline analysis. Sensitivity analysis was constructed through stratified analysis and interaction analysis.

About 1,440 stroke patients were included in this study. An elevated ALI was significantly related to a reduced risk of all-cause mortality in stroke patients but not related to CVD mortality. A reverse J-shaped non-linear association between ALI and all-cause mortality in stroke patients, with an inflection point at 83.76 (the lowest of the mortality risk). On the left side of the inflection point, for each 10 U increase in ALI, there was a 16% reduction in the risk of all-cause mortality. However, on the right side, the risk increased by 6%. There was no remarkable interaction between stratified variables and ALI.

The study concluded that elevated ALI was closely associated with a reduced risk of all-cause mortality in stroke patients, indicating a potential prognostic significance. The observed reverse J-shaped non-linear relationship existed between the 2, with an inflection point at 83.76, emphasizing the importance of maintaining ALI within an appropriate range for improved prognosis.

These findings suggest the necessity of interventions such as weight management, albumin supplementation, and anti-inflammatory treatment to control ALI in stroke patients. Furthermore, the dynamic variation in ALI offers a promising avenue for clinicians to establish personalized criteria, potentially enhancing long-term survival outcomes for stroke patients.

This study was sponsored by the Quanzhou Science and Technology Bureau, Quanzhou, China, the Natural Science Foundation of Fujian Province, and Joint funds for the innovation of science and technology, Fujian province.

Source: https://pubmed.ncbi.nlm.nih.gov/38699426/

Chen X, Hong C, Guo Z, et al (2024). “Association between advanced lung cancer inflammation index and all-cause and cardiovascular mortality among stroke patients: NHANES, 1999-2018.” Front Public Health. 2024 Apr 18;12:1370322. doi: 10.3389/fpubh.2024.1370322. PMID: 38699426; PMCID: PMC11063327.

CD8+ MAIT Cells: Predictive Biomarker in NSCLC Immunotherapy

KEY TAKEAWAYS

  • The study aimed to explore MAIT cells’ immune characteristics in NSCLC and their correlation with immune checkpoint inhibitor treatment efficacy.
  • The study’s findings revealed that CD8+ MAIT cells have the potential to predict the response to anti-PD-1 therapy in NSCLC patients.

While Mucosal-associated invariant T (MAIT) cells are known to modulate tumor immunity, their immune profile in non-small cell lung cancer (NSCLC) and their relationship with immune checkpoint inhibitor (ICI) efficacy remain unclear.

Jingjing Qu and the team aimed to investigate MAIT cell immune characteristics in NSCLC and their association with immune checkpoint inhibitor efficacy.

The study utilized single-cell RNA sequencing (scRNA-seq), flow cytometry, and multiplex immunofluorescence assays to evaluate CD8+ MAIT cell proportions and characteristics. This assessment was conducted in patients with metastatic NSCLC who responded or did not respond to anti-PD-1 therapy. Survival analyses were then conducted to assess the impact of MAIT cell proportion and CXCR6 expression in patients with advanced NSCLC prognosis.

The results revealed that responders exhibited significantly higher proportions of activated and proliferating CD8+ MAIT cells in both peripheral blood mononuclear cells (PBMCs) and lung tissues before anti-PD-1 therapy. These cells displayed increased expression of cytotoxicity-related genes, including CCL4, KLRG1, PRF1, NCR3, NKG7, GZMB, and KLRK1.

Furthermore, responders’ peripheral and tumor-infiltrating CD8+ MAIT cells showed elevated CXCR6 expression. Similarly, CXCR6+ CD8+ MAIT cells from responders exhibited higher expression of cytotoxicity-related genes such as CST7, GNLY, KLRG1, NKG7, and PRF1.

Patients with CD8+ MAIT cells to CD8+ T cells ratio ≥15.1% and CXCR6+ CD8+ MAIT cells to CD8+ MAIT cells ratio ≥35.9% in peripheral blood demonstrated improved progression-free survival (PFS) post-immunotherapy. The potential role of CD8+ MAIT cells in lung cancer immunotherapy appeared to be mediated by classical/non-classical monocytes via the CXCL16-CXCR6 axis.

The study concluded that CD8+ MAIT cells hold promise as predictive biomarkers for patients with NSCLC responsive to anti-PD-1 therapy. High CXCR6 expression likely correlates with immunotherapy sensitivity.

Research was funded by the Natural Science Foundation of Zhejiang Province, the National Natural Science Foundation of China, and Zhejiang Provincial Clinical Research Center for Respiratory Disease.

Source: https://pubmed.ncbi.nlm.nih.gov/38698468/

Qu, J., Wu, B., Chen, L., et al. (2024). “CXCR6-positive circulating mucosal-associated invariant T cells can identify patients with non-small cell lung cancer responding to anti-PD-1 immunotherapy.” J Exp Clin Cancer Res 43, 134 (2024). https://doi.org/10.1186/s13046-024-03046-3

Faecalibacterium prausnitzii Linked to Better NSCLC Survival

KEY TAKEAWAYS

  • The NADIMII phase 2 trial aimed to analyze F. prausnitzii’s potential as a cancer preventative in patients with NSCLC.
  • The results revealed that the F. prausnitzii presence was associated with improved survival in patients with NSCLC.

Aprominent member of the gut microbiota, Faecalibacterium prausnitzii is known for its significant contribution to butyrate production in the gastrointestinal tract. Recent research indicates that F. prausnitzii may also inhibit tumor development.

Alejandro Rodriguez-Festa and the team aimed to investigate the potential antitumorigenic effects of F. prausnitzii in non-small cell lung cancer (NSCLC).

In the phase II NADIM II clinical trial, researchers collected 81 baseline stool samples from patients with locally advanced NSCLC. These patients were randomized into 2 groups as the experimental arm (n=55), which received neoadjuvant nivolumab plus chemotherapy followed by adjuvant nivolumab, and the control arm (n=26), which received chemotherapy alone.

Stool samples were processed for DNA extraction using the QIAamp PowerFecal DNA Kit (Qiagen) and subjected to analysis via quantitative polymerase chain reaction (QPCR) utilizing specific primers designed for targeting F. prausnitzii strain ATCC 27768.

The presence of F. prausnitzii showed a significant association with improved overall survival (HR: 0.24; 95% CI: 0.08-0.76; P=0.015), with a trend towards progression-free survival (PFS) (HR: 0.46; 95% CI: 0.18-1.19; P=0.1). Specifically, among patients with detected F. prausnitzii in their fecal sample (n=46), 88% were alive and 68% showed no evidence of disease, compared to 55% and 44%, respectively, in patients without detectable F. prausnitzii (n=9).

Notably, this effect was not observed in the control group (P=0.425 for progression-free survival and P=0.812 for overall survival). A trend was also noticed in relation to PD-L1 expression, with 66% of tumors expressing PD-L1 in patients with detected F. prausnitzii, compared to 29% in the F. prausnitzii-negative group (P=0.062).

The study concluded that the presence of Faecalibacterium prausnitzii is linked to enhanced survival outcomes in patients with locally advanced NSCLC undergoing perioperative treatment with nivolumab and chemotherapy.

The trial was sponsored by the Fundación GECP.

Source: https://oncologypro.esmo.org/meeting-resources/european-lung-cancer-congress-2024/faecalibacterium-prausnitzii-enhances-tumor-response-to-perioperative-nivolumab-and-chemotherapy

Clinical Trial: https://clinicaltrials.gov/study/NCT03838159

Rodriguez-Festa A, Serna-Blasco R, Nadal E, et al. (2024). “Faecalibacterium prausnitzii enhances tumor response to perioperative nivolumab and chemotherapy.” Presented at ELCC 2024. Annals of Oncology (2024) 9 (suppl_3): 1-12. 10.1016/esmoop/esmoop102573 (138P)

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