Non Small Cell Lung Cancer

The expression of pre-treatment eHSP90α has significant significance for the prognosis and efficacy evaluation of driver-gene-negative NSCLC.

P1/2, N=34, Terminated, Pfizer | Active, not recruiting --> Terminated; Study was terminated due to portfolio re-prioritization and strategic considerations. The decision was not based on any safety concerns and/or regulatory interactions

P1/2, N=344, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Aug 2025 --> Apr 2026 | Trial primary completion date: Aug 2025 --> Apr 2026

P1/2, N=480, Recruiting, Parabilis Medicines, Inc. | N=245 --> 480

P=N/A, N=472, Recruiting, Scientific Institute San Raffaele

P4, N=6, Completed, Radboud University Medical Center | Phase classification: P2 --> P4

The case provides additional support that IT pemetrexed can offer symptomatic relief and may be considered as a treatment option in advanced LM. Furthermore, the case illustrates that an increased dose of lorlatinib may efficiently control LM in patients with ALK-rearranged NSCLC, following progression on standard lorlatinib dosage.

IGF2BP2 recognizes and stabilizes LOX1 through m6A modification, contributing to TAN-mediated LUAD progression. Overall, these findings offer new insights into LUAD progression and demonstrate that IGF2BP2 is a key regulator that promotes tumor advancement, highlighting the IGF2BP2-LOX1 axis as a potential therapeutic target for LUAD.

P=N/A, N=800, Completed, Jinling Hospital, China

P1, N=200, Recruiting, BeiGene | Active, not recruiting --> Recruiting | N=37 --> 200 | Trial completion date: May 2026 --> Dec 2026 | Trial primary completion date: May 2025 --> Dec 2026

P1, N=163, Active, not recruiting, AbbVie | Trial completion date: Mar 2025 --> Sep 2025 | Trial primary completion date: Mar 2025 --> Sep 2025

While NSCLC survival in Greenland has improved over the past decade, significant challenges remain. The trend towards diagnosing more stage IA-IIIA patients and the recent improvements in diagnostic and therapeutic options in Greenland are expected to translate into a better prognosis in the coming years. Addressing diagnostic delays and enhancing treatment options are crucial steps toward improving outcomes for NSCLC patients in Greenland.

P2, N=27, Not yet recruiting, Fudan University

P1, N=260, Active, not recruiting, ADC Therapeutics S.A. | Recruiting --> Active, not recruiting

Potential positive causal relationships were observed with Urate (β=0.012, P=0.020, FDR=0.180), urea (β=0.010, P=0.046, FDR=0.141), and glycated hemoglobin HbA1c (β=0.020, P=0.049, FDR P=0.098), whereas a potential negative causal relationship was observed with sex hormone-binding globulin(SHBG) (β=-0.020, P=0.036, FDR=0.108).Lastly, adenocarcinoma was found to have a positive causal association with alkaline phosphatase (β=0.015, P=0.006, FDR=0.033*). Our study provides a robust theoretical basis for the early screening and therapeutic monitoring of lung cancer and contributes to understanding the pathogenesis of the disease.

This study highlights the crucial role of CTSL as a prognostic biomarker in LUAD. This combined multicenter and omics-based analysis provides comprehensive insights into the biological role of CTSL, supporting its potential as a target for therapeutic intervention and a marker for prognosis in patients with LUAD.

However, due to the paucity of solid data from randomized, controlled phase III clinical studies, clinicians often require more systematic, real-world data-based guidance for its optimal clinical use. As one of the leading countries of real-world research on crizotinib, China has contributed significantly to data on standardization of the therapeutic use of crizotinib, including its clinical treatment patterns, the timing and duration of treatment and drug resistance monitoring and management.

The top 10 mutations that most commonly accompanied PIK3CA variations were KRAS, NF1, TP53, EGFR, PTEN, BRAF, KIT, CDKN2A, SMARCA4, and ATM mutations, respectively. PIK3CA variations, along with other gene variations, may influence cancer progression and thus may play a crucial role in the determination of targeted treatment strategies.

Immunotherapies, alone or in combination with other treatments, have demonstrated promising results in NSCLC with BMs, although most clinical trials have included only selected patients with asymptomatic or previously treated BMs. In this review, we discuss the molecular and immune characteristics of NSCLC with BMs, analyze intracranial efficacy findings from clinical trials, and explore treatment strategies for lung cancer patients with BMs.

However, resistance to BRAF pathway inhibitors is inevitable, leading to disease progression, and a well-defined strategy to overcome these resistance mechanisms is lacking. This review aims to explore the critical challenges in the management of BRAF-mutated NSCLC, providing a comprehensive summary of the current evidence and highlighting ongoing clinical trials that aim to address these critical gaps.

In conclusion, hypoxia-induced radioresistance is present despite the absence of functional p53. This resistance is related to differences in clonogenicity, cell cycle regulation, cytokine secretion, and gene expression under chronic hypoxia, but not to differences in DNA DSB repair kinetics.

In HCF-aa under RES, increased exosomal MALAT1 expression counteracts miR-499-5p's suppression of SOX6, suggesting that MALAT1-containing exsosomes derived from HCF-aa may offer a novel cell-free therapeutic approach for AF.

Here, using two separate approaches to displace V3 from microtubules and a variety of in vitro assays, we show that microtubule association of EML4-ALK V3 is required for both V3 phenotypes, as removal of the oncogenic fusion protein from microtubules led to the dissociation of the V3-NEK9-NEK7 complex and the reversal of both phenotypic changes. Overall, we propose that targeting the interaction between EML4-ALK V3 and microtubules might offer a novel therapeutic option, independent of ALK activity, for V3+ NSCLC patients with acquired resistance to ALK inhibitors.

Circulating miRNAs hold strong potential for the early detection of LC and for distinguishing LC from TB.

This subgroup of IO-responsive NS-pts may have better prognosis. Our findings suggest that DDR-based mutational profiling may help identify NS-pts who could benefit from IO therapy.

Lung cancer is one of the leading causes of cancer-related death worldwide [...].

The major translational relevance of this study is to exploit new targets for the development of innovative and improved therapeutic strategies with NOA drugs, over combinations including target genes within the oncogene pathway, to overcome resistance to TKI therapies in patients with NSCLC who are oncogene-addicted.

Overexpression of MALAT1 in Sertoli cells did not induce apoptosis but impaired their cell supporting function. In conclusion, MALAT1 overexpression in SSCs contributes to the pathogenesis of iNOA via downregulating ETV5 expression and promoting cell apoptosis.

Considering the frailty associated with cachexia, ICI monotherapy may be preferred to ICI/chemotherapy for these patients. New interventions that can better address the negative prognostic impact of cachexia in patients treated using ICIs with or without chemotherapy remain warranted.

KRAS inhibitors and other emerging alternative treatments are also discussed, as combining these drugs with immunotherapy may serve as a promising first-line treatment for KRAS-mutated NSCLC in the future. We hope that this review will assist in first-line treatment choices and shed light on the development of novel agents for KRAS-mutated NSCLC.

Our results indicated that TFAP2A activates fatty acid metabolism by positively modulating the expression of CTHRC1, thereby facilitating tumor cells' migration and invasion. These findings provided novel insights into LAC treatment and future research.

Taken together, our work uncovers a new mechanism by which ShtIX induced ferroptosis through inhibition the Nrf2 pathway and activation of NCOA4-mediated ferritinophagy in NSCLC cells. Targeting ferritinophagy to regulate ferroptosis offers a novel therapeutic strategy for the treatment of lung cancer with ShtIX.

Combining cases from our oncology center and previous literature, we found that NSCLC patients with coexisting ALK fusion mutations and other mutations have poorer response to targeted therapy and poorer prognosis, and we also compared the efficacy rates of various types of coexisting mutations for different treatment regimens. Therefore, this review can help to evaluate the prognosis of NSCLC patients with coexisting mutations and the efficacy of targeted therapies and to find more favorable treatment options for patients with this type of coexisting mutations.

The study suggests that hybrid scaffolds combining key pharmacophoric features from Osimertinib and Brigatinib along with Lys745 targeting warheads, could enhance selectivity and potency. Fourth-generation TKIs targeting Lys745 offer a novel therapeutic avenue, potentially overcoming mutation-induced resistance and improving NSCLC treatment outcomes. This approach represents a critical advancement toward durable clinical responses in patients with drug-resistant cancer.

The potential targets and molecular mechanisms of THSWD in the treatment of NSCLC were preliminarily revealed by a comprehensive analysis in this study, which will provide new ideas and methods for the study of the mechanism of traditional Chinese medicine in treating lung cancer.

Finally, the ALKBH5-FBXL5 axis reduces intracellular reactive oxygen species levels, leading to PI3K/AKT and NF-kB pathway inhibition and consequently suppresses NSCLC proliferation and metastasis in vitro and in vivo. Triggered by an insertion variant, this remote cis-regulation of m6A eraser and the downstream molecular events modulate the survival of NSCLC patients.

Targeting LDHA and disrupting lactate metabolism and its signaling pathways can effectively enhance the sensitivity of LUAD to Lobaplatin, providing a promising approach to overcoming multidrug resistance. These findings offer valuable insights into developing new treatment strategies for lung adenocarcinoma, emphasizing the role of metabolic pathways in cancer therapy.

This prodrug demonstrates superior safety compared to natural DON and greater antitumor activity against resistant tumors compared to the clinical phase II drug DRP104. These findings may address the clinical limitations of GLS1 allosteric inhibitors and underscore prodrug strategies in effectively treating Osimertinib-resistant lung cancer, providing a foundation for future clinical trials.

The differentially expressed lncRNAs, especially MALAT1, may act as ceRNA via sponging miRNAs and to regulate the targeting downstream mRNAs in development of PMC and participate in numerous biological processes through interconnected signaling pathways.

The patient, now on combination therapy for exceeding 12 months, exhibits further decreased tumor size and a high quality of life. This case underscores the importance of precise molecular diagnosis in guiding therapeutic strategies and provides a valuable reference for clinical decision-making in EGFR-positive NSCLC cases with atypical mutations.

The DCA showed that when it comes to EGFR mutation status prediction, the nomogram and the radiomics model showed better overall net benefit than the radiographic model. For preoperatively predicting the status of EGFR mutation in lung adenocarcinomas manifesting as GGNs, the CT-based radiomics analysis will be valuable.

Furthermore, we found that the expression of cuproptosis genes (DLAT, DLD, and PDHA1) was positively correlated with the expression of PSMD11 (P<0.001). These results indicate that PSMD11 has the potential to be a novel therapeutic target and sensitive biomarker for patients with LUAD.