New promises and challenges in the treatment of advanced non-small-cell lung cancer

The Lancet, Год журнала: 2024, Номер 404(10454), С. 803 - 822

Опубликована: Авг. 1, 2024

Язык: Английский

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Update 2025: Management of Non‑Small-Cell Lung Cancer

Lung, Год журнала: 2025, Номер 203(1)

Опубликована: Март 25, 2025

Lung cancer remains the leading cause of cancer-related mortality worldwide. Since 2024, non-small-cell lung (NSCLC) landscape has undergone a transformative shift, driven by 11 FDA approvals. Recent advances in molecular profiling, targeted therapies, and immunotherapies have revolutionized NSCLC management, ushering an era personalized treatment with improved patient outcomes. The increased adoption low-dose computed tomography (LDCT) for screening enhanced early detection, enabling intervention at more curable stages. Molecular diagnostics now play pivotal role guiding strategies, actionable genomic alterations (AGAs) informing use EGFR, ALK, ROS1, KRAS, NRG1, other inhibitors both advanced settings. For instance, therapies are increasingly being integrated into early-stage adjuvant osimertinib EGFR-mutated alectinib ALK-positive demonstrating substantial survival benefits. Immunotherapy, particularly immune checkpoint inhibitors, become cornerstone AGA-negative NSCLC, either as monotherapy or combination chemotherapy, is utilized perioperative setting. Furthermore, emerging such bispecific antibodies, antibody-drug conjugates (ADCs), novel immunotherapeutic agents show promise addressing resistance mechanisms improving outcomes advanced-stage disease. Although new challenges arise, evolving paradigm continues to prioritize precision medicine, offering hope prolonged quality life patients.

Язык: Английский

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circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC)

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Май 7, 2024

Abstract Background Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence development a variety tumors. The aim this study was to investigate effects circ_PPAPDC1A Osimertinib resistance NSCLC. Methods Human circRNAs microarray analysis conducted identify differentially expressed (DE) Osimertinib-acquired tissues effect on cell proliferation, invasion, migration, apoptosis assessed both vitro vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, rescue assay were employed confirm interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. Results results revealed significantly upregulated acquired reduced sensitivity PC9 HCC827 cells promoted while inhibiting Osimertinib-resistant PC9/OR HCC829/OR cells, Silencing partially reversed resistance. Additionally, acted as competing endogenous (ceRNA) by targeting miR-30a-3p, Insulin-like Growth Factor 1 Receptor (IGF1R) identified functional gene for miR-30a-3p Furthermore, confirmed axis plays role activating PI3K/AKT/mTOR signaling pathway NSCLC with Conclusions Therefore, first time we exerts an oncogenic sponging active IGF1R/PI3K/AKT/mTOR pathway. may serve novel diagnostic biomarker therapeutic target patients Graphical

Язык: Английский

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Allostery in Disease: Anticancer Drugs, Pockets, and the Tumor Heterogeneity Challenge

Journal of Molecular Biology, Год журнала: 2025, Номер unknown, С. 169050 - 169050

Опубликована: Фев. 1, 2025

Язык: Английский

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Drug Resistance in Late-Stage Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer Patients After First-Line Treatment with Tyrosine Kinase Inhibitors

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 2042 - 2042

Опубликована: Фев. 26, 2025

The development of tyrosine kinase inhibitors (TKIs) for late-stage epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) represented a drastic change in the treatment cancer. Drug resistance develops after certain period first-line TKI treatment, which has led to decades changing guidelines EGFR-mutant NSCLC. This study discussed potential mechanisms drug against and successive strategies. Next-generation sequencing (NGS) may play role evaluation treatment. Emerging combination regimens ongoing trials were discussed. Potential future strategies management proposed this study.

Язык: Английский

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Panduratin A from Boesenbergia rotunda Effectively Inhibits EGFR/STAT3/Akt Signaling Pathways, Inducing Apoptosis in NSCLC Cells with Wild-Type and T790M Mutations in EGFR

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 2350 - 2350

Опубликована: Март 6, 2025

Non-small cell lung cancer (NSCLC) is a challenging disease, with the epidermal growth factor receptor (EGFR) being key target for new, effective treatments crucial signaling pathways regulating survival. Targeting EGFR-mediated offers promising strategies to improve NSCLC therapies, particularly in overcoming resistance EGFR-mutant cancer. In this study, we investigated anticancer effects of panduratin A, naturally occurring flavonoid from Boesenbergia rotunda, on human lines expressing both wild-type EGFR (A549) and mutant (H1975) using vitro experiments molecular docking approaches. Cytotoxicity screening revealed that A exhibits potent A549 (IC50 6.03 ± 0.21 µg/mL) H1975 5.58 0.15 while demonstrating low toxicity normal MRC5 cells (12.96 0.36 µg/mL). Furthermore, western blotting flow cytometric analyses indicated induces apoptosis by inhibiting p-EGFR its downstream effectors, p-STAT3 p-Akt, cells. Additionally, study showed lower binding energy between proteins, comparable tyrosine kinase inhibitors (EGFR TKIs). The ADMET prediction also highlighted A's exceptional drug-like properties. This concludes shows significant promise as an anti-lung candidate NSCLC, offering economical strategy.

Язык: Английский

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Lung Cancer Research and Treatment: Global Perspectives and Strategic Calls to Action

Annals of Oncology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

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Antibody-drug conjugates in NSCLC with actionable genomic alterations: Optimizing smart delivery of chemotherapy to the target

Cancer Treatment Reviews, Год журнала: 2025, Номер 134, С. 102902 - 102902

Опубликована: Фев. 16, 2025

Язык: Английский

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Treatment of lung diseases via nanoparticles and nanorobots: Are these viable alternatives to overcome current treatments?

Materials Today Bio, Год журнала: 2025, Номер 31, С. 101616 - 101616

Опубликована: Фев. 26, 2025

Язык: Английский

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Oncogenic KRASG12D Transfer from Platelet-like Particles Enhances Proliferation and Survival in Non-Small Cell Lung Cancer Cells

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3264 - 3264

Опубликована: Апрель 1, 2025

In the tumor context, platelets play a significant role in primary progression, dissemination and metastasis. Analysis of this interaction various cancers, such as non-small cell lung cancer (NSCLC), demonstrate that can both transfer receive biomolecules (e.g. RNA proteins) to from at different stages, becoming tumor-educated platelets. To investigate how are able oncogenic material, we developed vitro platelet-like particles (PLPs), differentiated MEG-01 line, stably carry protein KRASG12D oncogene fusion with GFP. We co-cultured these PLPs NSCLC H1975 cells assess their ability material. observed generated were capable expressing transferring its forms using qPCR imaging techniques. Additionally, found coculturing loaded GFP-KRASG12D increased proliferative capacity specific PLP concentrations. conclusion, our study successfully engineered an line produce carrying simulating microenvironment, demonstrating efficient impact on enhancing proliferation.

Язык: Английский

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