Non Small Cell Lung Cancer

The discontinuation rate was significantly lower in patients who consulted a PLOC pharmacist than for those who did not (73% vs 97%, p = 0.008). However, the rates and reason for osimertinib discontinuation or dose reduction did not differ between groups.ConclusionPLOC consultation and intervention for the treatment of adverse events might have led to extending the duration of osimertinib treatment.

Knockdown of one of these genes, Notch homolog protein 3, simulates the anti-angiogenic effects of miR-1. These findings suggest that miR-1 can be used as an indicator of malignant transformation.

TIMER-based correlation analysis demonstrated a positive association between RBMS3 expression and immune cell infiltration, with the regression line indicating significant correlations for B cells (cor = 0.16, P = 4.25 × 10⁻4), CD8 + T cells (cor = 0.214, P = 1.86 × 10⁻⁶), CD4 + T cells (cor = 0.24, P = 8.99 × 10⁻⁸), macrophages (cor = 0.341, P = 1.07 × 10⁻14), neutrophils (cor = 0.277, P = 5.71 × 10⁻10), and dendritic cells (cor = 0.369, P = 3.70 × 10⁻17). These findings underscore RBMS3's dual role in LUAD as a tumor suppressor and immune microenvironment modulator, offering novel insights for prognosis and therapy.

BBR hindered NSCLC cell malignant progression partly by modulating CDCA5 and CCNA2, providing a promising therapeutic target for NSCLC treatment.

This study provides the first evidence of cisplatin concentration-dependent metabolic reprogramming during NSCLC-to-SCLC transformation. We identified a phenotypic transition from NSCLC to SCLC accompanied by a metabolic shift from glucose to fatty acid metabolism, offering new insights into therapeutic strategies for treatmentresistant lung cancer.

The combination of TKI/chemotherapy (osimertinib/carboplatine-pemetrexed) and TKI/bispecific antibodies (e.g., amivantamab/lazertinib) are alternatives under evaluation, with benefits in PFS but increased toxicity. Other emerging approaches include conjugated antibodies (patritumab deruxtecan, datopotamab deruxtecan) and next-generation TKIs. In the future, personalized treatment based on the molecular profile and early response to TKIs could optimize management, particularly by integrating predictive markers such as EGFR clearance under treatment.

Testing of these alterations is therefore recommended on surgical specimens and, where appropriate, on pre-treatment biopsies. Many questions remain with regards to the implementation of these strategies: duration of treatment, treatment in case of recurrence, impact on molecular evolution.

However, the emergence of complex resistance mechanisms, whether ALK-dependent or ALK-independent, remains a major challenge. The comprehensive understanding of these resistance mechanisms now guides the development of next-generation inhibitors and innovative therapeutic strategies, paving the way for increasingly personalized precision medicine.

These new molecules lead to new side effects we will have to manage, such as the Cytokine Relargage Syndrome. Other molecules, targeting DLL3 or other pathways are still ungoing clinical evaluation, we should see further advances in the treatment of SCLC over the coming years.

In this review, we discuss the targeted therapies available in France and the promising future molecules for managing rare oncogenic drivers. Targeted therapies have already proven their efficacy as first-line treatments for ROS-1 and RET alterations, and as second-line treatments for MET and BRAF mutations.

GABA-B1 receptors were down-regulated in lung adenocarcinoma cells. Non-specific activation of the GABA-B receptor by baclofen significantly inhibited lung adenocarcinoma cell proliferation by cell cycle arrest and suppressed the GSK3 signaling pathway.

These findings highlight LCCP's potential to improve personalized treatment strategies for NSCLC.

The incidence of thyroid dysfunction was significantly higher in patients treated with atezolizumab compared to pembrolizumab (P = 0.04), with 87.5% of affected patients receiving atezolizumab. These findings suggest that thyroid dysfunction is a common irAE in patients with metastatic NSCLC receiving ICIs, particularly atezolizumab, and its development may be associated with improved PFS. Regular monitoring of thyroid function is recommended to promptly identify and manage thyroid abnormalities during ICI therapy, potentially improving patient outcomes.

We demonstrate an association between a polygenic risk score for autoimmune disease and early ICI discontinuation for irAEs. Our results suggest that germline genetics may be used as an adjunctive tool for risk stratification around ICI clinical decision-making in solid tumor oncology.

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We evaluated the efficacy and safety of lorlatinib in ALK- and ROS1-positive NSCLC patients within a compassionate use program in Spain. Among 61 ALK-positive patients, including 59 % with brain metastasis and 85.2 % treated with at least 2 prior ALK TKIs, lorlatinib achieved a confirmed overall response rate (ORR) of 32.8 % and a median progression-free survival (PFS) of 11.2 months. In 42 ROS1-positive patients previously treated with crizotinib, lorlatinib showed an ORR of 47.6 % and a median PFS of 10 months, confirming its clinical activity despite the lack of FDA or EMA approval for this indication.

There is limited published evidence on the use of olaparib in patients harboring pathogenic variants other than breast cancer genes, like PALB2 and ATM and conditions different than those authorized such as digestive tract, neuroendocrine and lung tumors. Further research is to assess the efficacy of olaparib in these patients.

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Most prominent alterations were observed in EGFR (auto-phosphorylation Y1197 and 10 bi- and triantennary fucosyl-sialo glycans at N603), downstream PI3K-Akt pathway (ERBB2-T1240, MET-S990/T992, AKT-S124/S126) and integrin family (sialo-fucosyl glycans), suggesting site-specific alteration between N-glycosylation and phosphorylation interplay in the TKI resistant L858R-T790M mutant NSCLC cells. The glycoproteomic and phosphoproteomic landscape may help to unravel the complex modification alterations underlying the resistant mechanism, offering insights for improving therapeutic strategies and patient outcomes.

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This review delves into the current clinical status, efficacy, safety profiles, and regulatory approvals of third-generation EGFR TKIs, including Osimertinib, Lazertinib, Furmonertinib, Aumolertinib, Rezivertinib, Befotertinib, Sunvozertinib...Notable fourth-generation candidates such as TQB3804, BPI-361175, BDTX-1535, WJ13404, QLH11811, H002, HS-10375, BBT-207, JIN-A02, and HS-10504 are highlighted for their potential to overcome the C797S mutation...By evaluating the therapeutic potential and limitations of these EGFR TKIs, this review aims to guide future research in the management of EGFR-mutant NSCLC. This acts as guiding beacon for the strategic design and development of third and fourth generation EGFR-TK inhibitors to overcome the drug resistance hurdles in the development of EGFR-TK inhibitors.

Encouraging and durable antitumor activity was observed with Dato-DXd in this heavily pretreated advanced/metastatic NSCLC population with actionable genomic alterations. The rate of treatment-related grade ≥3 toxicities was comparable with previous observations, and no new safety signals were observed.

P2, N=227, Active, not recruiting, Maia Biotechnology | Trial primary completion date: Aug 2025 --> Dec 2025

tsRNA-49-73-Glu-CTC has the potential to serve as a novel molecular diagnostic biomarker for NSCLC and plays a significant role in the biological processes associated with NSCLC proliferation and migration.

To assess the efficiency of DNA DSB repair, we analyzed the quantitative yield of residual foci of DSB marker proteins (γH2AX and 53BP1) 24 h after irradiation with doses of 2, 4, and 6 Gy. The results showed that co-cultivation with MSCs did not affect the efficiency of DNA DSB repair induced by X-rays, as well as the proliferative activity of NSCLC cells.

P=N/A, N=320, Active, not recruiting, Instituto Nacional de Cancerologia, Columbia

P3, N=577, Active, not recruiting, Mirati Therapeutics Inc. | Trial completion date: Dec 2024 --> Jun 2025

P3, N=611, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Sep 2029 --> Aug 2026 | Trial primary completion date: Sep 2028 --> Aug 2026

The few patients who received IO in 1L and 2L had favorable rwPFS and OS. Future research on sequential IO therapies in 1L and 2L aNSCLC is warranted.

This study demonstrates that PLIN3 contributes to DDP resistance in LUAD by activating the Wnt3a/β-catenin signaling pathway, with FOSL1 acting as a critical upstream regulator. Targeting the FOSL1/PLIN3/Wnt/β-catenin axis may provide a promising therapeutic strategy for overcoming chemoresistance in LUAD.

Conversely, miR-17-5p inhibition elevated lncRNA-FGD5-AS1 levels and reversed these effects.ConclusionThe findings identify the miR-17-5p/lncRNA-FGD5-AS1 regulatory axis as a novel therapeutic target for NSCLC. By integrating molecular and technological approaches, this study offers insights into precision oncology and highlights the potential for advanced RNA-based interventions.

In all, we conducted an in-depth analysis of the molecular characteristics and transformation mechanisms of MIP-LUAD, employing microdissection techniques to investigate the genomic and transcriptomic levels within a substantial cohort, providing insights for precision medicine of this aggressive cancer subtype.

Functional analyses showed that LA significantly promoted tumor growth in vitro and in vivo while conferring increased resistance to alectinib...These findings establish LOC388942-ALK as a novel oncogenic driver in lung cancer, highlighting its role in tumor growth and ALK inhibitor resistance. Targeting FOS may provide a promising therapeutic strategy for tumors harboring this intergenic fusion.

These data highlight the variability of MAGE-A4 expression across different cancer types and underscore its relevance as a potential target of novel precision medicines. The significant presence of MAGE-A4 in specific cancers suggests potential for stratified therapeutic approaches and warrants further investigation into its role in oncogenesis and treatment response.

Furthermore, CISD1 has potential applications in immunotherapy. These findings may provide novel theoretical insights into the treatment of LUAD.