Oncogenic alterations in advanced NSCLC: a molecular super-highway

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Feb. 12, 2024

Lung cancer ranks among the most common cancers world-wide and is first cancer-related cause of death. The classification lung has evolved tremendously over past two decades. Today, non-small cell (NSCLC), particularly adenocarcinoma, comprises a multitude molecular oncogenic subsets that change both prognosis management disease.Since targeted alteration identified in 2004, with epidermal growth factor receptor (EGFR), there been unprecedented progress identifying targeting new alterations. Almost decades experience have allowed scientists to elucidate biological function drivers understand often overcome basis acquired resistance mechanisms. targetable alterations are approximately 60% adenocarcinoma patients Western populations 80% Asian populations. Oncogenic largely enriched non-smokers, east Asians, younger patients, though each its own patient phenotype.The current landscape druggable targets includes EGFR, anaplastic lymphoma kinase (ALK), v-raf murine sarcoma viral oncogene homolog B (BRAF), ROS proto-oncogene 1 (ROS1), Kirstin rat virus (KRAS), human 2 (HER2), c-MET (MET), neurotrophic tyrosine (NTRK), rearranged during transfection (RET), neuregulin (NRG1). In addition these known targets, others including Phosphoinositide 3-kinases (PI3K) fibroblast (FGFR) garnered significant attention subject numerous ongoing trials.In this era personalized, precision medicine, it paramount importance identify or potential patient. development therapy mirrored by diagnostic progress. Next generation sequencing offers high-throughput, speed breadth entire genomes regions DNA RNA. It for identification majority unique window into novel alterations, de novo mechanisms.In review, we discuss approach advanced NSCLC, focusing on driver through their pathophysiology, management, future perspectives. We also explore shortcomings hurdles encountered rapidly evolving field.

Language: Английский

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Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer: A Phase II Multicenter Study

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(26), P. 3105 - 3114

Published: July 19, 2024

To assess the safety and efficacy of third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA

Language: Английский

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Phase II Study of Atezolizumab and Bevacizumab Combination Therapy for Patients with Advanced Hepatocellular Carcinoma Previously Treated with Lenvatinib

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 278 - 278

Published: Jan. 16, 2025

Background/Objectives: Atezolizumab and bevacizumab combination therapy has been established as a standard of care for first-line treatment; however, its efficacy safety have not fully evaluated patients previously treated with systemic therapy. Methods: In this phase II trial, advanced hepatocellular carcinoma lenvatinib were enrolled to receive dose 1,200 mg atezolizumab 15 mg/kg every 3 weeks. The primary endpoint was progression-free survival. secondary endpoints included overall survival, objective response rate, disease control subsequent therapy, frequency adverse events. threshold expected survival 6.8 months, respectively. Considering one-sided significance level 0.05 statistical power 80%, the minimum required sample size 26 patients. Results: median from start treatment 9.70 [90% confidence interval, 5.10-14.24] lower limit 90% CI above predefined threshold. rates 34.6% 73.1%, Sixteen (61.5%) received therapies, 17.23 13.18-27.85] months. Severe events, events leading delays, discontinuation occurred in eight (30.8%), fourteen (53.8%), five (19.2%) patients, respectively, no treatment-related deaths occurred. Conclusions: is effective can safely be administered HCC lenvatinib.

Language: Английский

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Management of locally advanced non‐small cell lung cancer: State of the art and future directions

Cancer Communications, Journal Year: 2023, Volume and Issue: 44(1), P. 23 - 46

Published: Nov. 20, 2023

Abstract Lung cancer is the second most common and deadliest type of worldwide. Clinically, non‐small cell lung (NSCLC) pathological cancer; approximately one‐third affected patients have locally advanced NSCLC (LA‐NSCLC, stage III NSCLC) at diagnosis. Because its heterogeneity, LA‐NSCLC often requires multidisciplinary assessment. Moreover, prognosis much below satisfaction, efficacy traditional therapeutic strategies has reached a plateau. With emergence targeted therapies immunotherapies, as well continuous development novel radiotherapies, we entered an era treatment paradigm for LA‐NSCLC. Here, reviewed landscape relevant modalities, including adjuvant, neoadjuvant, perioperative immune in with resectable with/without oncogenic alterations; combinations chemoradiation immunotherapy/targeted therapy unresectable We addressed unresolved challenges that remain field, examined future directions to optimize clinical management increase cure rate

Language: Английский

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Immunotherapy resistance in solid tumors: mechanisms and potential solutions

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: Feb. 22, 2024

While the emergence of immunotherapies has fundamentally altered management solid tumors, cancers exploit many complex biological mechanisms that result in resistance to these agents. These encompass a broad range cellular activities - from modification traditional paradigms immunity via antigen presentation and immunoregulation metabolic modifications manipulation tumor microenvironment. Intervening on intricate processes may provide clinical benefit patients with tumors by overcoming immunotherapies, which is why it become an area tremendous research interest practice-changing implications. This review details major ways avoid both natural through primary (innate) secondary (acquired) resistance, considers available emerging therapeutic approaches immunotherapy resistance.

Language: Английский

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The changing treatment landscape of EGFR-mutant non-small-cell lung cancer

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 29, 2024

Language: Английский

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Combining Genomic Biomarkers to Guide Immunotherapy in Non–Small Cell Lung Cancer

Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 30(7), P. 1307 - 1318

Published: Feb. 1, 2024

The clinical value of STK11, KEAP1, and EGFR alterations for guiding immune checkpoint blockade (ICB) therapy in non-small cell lung cancer (NSCLC) remains controversial, as some patients with these proposed resistance biomarkers show durable ICB responses. More specific combinatorial biomarker approaches are urgently needed this disease.

Language: Английский

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Immunotherapy in Oncogene-Addicted NSCLC: Evidence and Therapeutic Approaches

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 583 - 583

Published: Jan. 11, 2025

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. The discovery specific driver mutations has revolutionized the treatment landscape oncogene-addicted NSCLC through targeted therapies, significantly improving patient outcomes. However, immune checkpoint inhibitors (ICIs) have demonstrated limited effectiveness in this context. Emerging evidence, though, reveals significant heterogeneity among different mutation subgroups, suggesting that certain subsets may benefit from ICIs, particularly when combined with other therapeutic modalities. In review, we comprehensively examine current evidence on efficacy immunotherapy NSCLC. By analyzing recent clinical trials and preclinical studies, along an overview mechanisms reduce efficacy, explored potential strategies to address these challenges, provide insights could optimize approaches integrate them effectively into algorithm for

Language: Английский

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The Whole Picture of First-Line Osimertinib for EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer: Real-World Efficacy, Safety, Progression Pattern, and Posttreatment Therapy (Reiwa Study)

JTO Clinical and Research Reports, Journal Year: 2024, Volume and Issue: 5(11), P. 100720 - 100720

Published: Sept. 7, 2024

Language: Английский

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QL1706 (anti-PD-1 IgG4/CTLA-4 antibody) plus chemotherapy with or without bevacizumab in advanced non-small cell lung cancer: a multi-cohort, phase II study

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 29, 2024

Abstract First-line chemoimmunotherapy (with or without bevacizumab) has improved outcomes in advanced non-small cell lung cancer (NSCLC). Here, this open-label, multi-cohort phase II study (NCT05329025) was done to investigate the safety and efficacy of QL1706 (a single bifunctional MabPair product against PD-1 CTLA-4) chemotherapy with bevacizumab population. Patients were enrolled into five different cohorts based on genotype (cohorts 1-4, epidermal growth factor receptor [EGFR] wild-type; cohort 5, EGFR-mutant progressed EGFR-tyrosine kinase inhibitors [TKIs]). Between June 11, 2021 December 29, 2021, 91 patients enrolled. Most frequent treatment-related adverse events (TRAEs) included decreased appetite (60 [65.9%]), anemia infusion-related reactions (48 [52.7%]), pruritus (44 [48.4%]). Grade ≥ 3 TRAEs occurred 30 (33.0%) patients. Twenty-seven (45%) wild-type EGFR achieved partial response (PR) (objective rate [ORR] = 45%) had a median progression-free survival (mPFS) 6.8 months (95% CI: 5.2-9.7). For 31 harboring mutated EGFR, 17 (54.8%) PR (ORR 54.8%), an mPFS 8.5 5.72-not evaluable). Overall, plus chemotherapy, regardless having bevacizumab, generally tolerable promising antitumor activity for NSCLC first-line setting. Moreover, showed favorable who but failed TKI therapy, demonstrating potential treating

Language: Английский

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