Therapy for Stage IV Non–Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.3

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(11), P. e1 - e22

Published: Feb. 28, 2024

To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer driver alterations.

Language: Английский

---

Six‐Membered Aromatic Nitrogen Heterocyclic Anti‐Tumor Agents: Synthesis and Applications

The Chemical Record, Journal Year: 2023, Volume and Issue: 23(12)

Published: Nov. 27, 2023

Cancer stands as a serious malady, posing substantial risks to human well-being and survival. This underscores the paramount necessity explore investigate novel antitumor medications. Nitrogen-containing compounds, especially those derived from natural sources, form highly significant category of agents. Among these, agents with six-membered aromatic nitrogen heterocycles have consistently attracted attention chemists pharmacologists. Accordingly, we present comprehensive summary synthetic strategies clinical implications these compounds in this review. entails an in-depth analysis synthesis pathways for pyridine, quinoline, pyrimidine, quinazoline. Additionally, historical progression, targets, mechanisms action, effectiveness small molecule inhibitors possessing structural features.

Language: Английский

---

Advancements in NSCLC

American Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 20, 2024

With the global incidence of non-small cell lung cancer (NSCLC) on rise, development innovative treatment strategies is increasingly vital. This review underscores pivotal role precision medicine in transforming NSCLC management, particularly through integration genomic and epigenomic insights to enhance outcomes for patients. We focus identification key gene mutations examine evolution impact targeted therapies. These therapies have shown encouraging results improving survival rates quality life. Despite numerous being identified association with NSCLC, treatments are available only a select few. paper offers an exhaustive analysis pathogenesis reviews latest advancements therapeutic approaches. It emphasizes ongoing necessity research this domain. In addition, we discuss current challenges faced clinical application these potential directions future research, including novel targets new modalities.

Language: Английский

---

Successful treatment with selpercatinib after pralsetinib-related pneumonitis and intracranial failure in a patient with RET-rearranged nonsmall cell lung cancer

Anti-Cancer Drugs, Journal Year: 2024, Volume and Issue: unknown

Published: March 8, 2024

Pralsetinib and selpercatinib are two highly potent selective rearranged during transfection (RET) inhibitors that substantially improved the clinical outcome of patients with RET-rearranged non-small cell lung cancer. Treatment one RET inhibitor after failure other is generally not recommended because cross-resistance mechanisms. We report case a patient affected by metastatic cancer who experienced long-lasting disease control pralsetinib. After 13 months from treatment start, developed recurrent drug-related pneumonitis, requiring temporary interruptions dose reductions eventually failing to disease. Selpercatinib was then started as an off-label treatment, allowing both radiological intracranial control. well-tolerated at full dosage, no pulmonary event occurred. In our report, pralsetinib reduction due toxicity, therapeutic switch allowed receive full-dose restoring Our few literature data suggest switching may represent opportunity, especially for brain metastases.

Language: Английский

---

Assessment of Exhaled Breath Condensate for ALK, RET, ROS1, and NTRK1 Fusion Transcript Detection in NSCLC: Comparison With Tissue and Liquid Biopsy Samples

Thoracic Cancer, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 1, 2025

ABSTRACT Background Lung cancer continues to be the primary cause of cancer‐related deaths globally, with majority cases identified at advanced stages. Genetic alterations, including mutations and gene fusions, are central its molecular pathogenesis. The discovery therapeutically targetable such as ALK , RET ROS1 NTRK1 has significantly lung management. Conventional methods, tissue biopsies, invasive unsuitable for continuous monitoring. Consequently, noninvasive approaches, liquid biopsies exhaled breath condensate (EBC), offer promising options real‐time surveillance. Methods This study evaluates feasibility identifying fusion transcripts in 30 patients adenocarcinoma by using next‐generation sequencing (NGS) on formalin‐fixed paraffin‐embedded (FFPE) tissue, plasma, EBC samples. Results Clinically significant transcripts, KIF5B‐ALK KIF5B‐RET SQSTM1‐ALK were detected across different sample types. samples showed strong concordance biopsy results, particularly detecting demonstrated greater sensitivity than plasma fusions. Additionally, uncertain clinical significance identified, highlighting need further research into their role Conclusion In conclusion, provide a valuable, medium clinically relevant previously uncharacterized non‐small cell (NSCLC). high between suggests that could complement effective diagnosis monitoring NSCLC. These findings underscore importance comprehensive profiling multiple types enhance diagnostic precision optimize therapeutic outcomes

Language: Английский

---

Safety, pharmacokinetics and efficacy of HA121-28 in patients with advanced solid tumors and RET fusion-positive non-small-cell lung cancer: a multicenter, open-label, single-arm phase 1/2 trial

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 27, 2025

Abstract HA121-28, a promising multikinase inhibitor, mainly targets rearranged during transfection (RET) fusions and selectively vascular endothelial growth factor receptor-2, receptor, fibroblast receptor 1-3. The safety, pharmacokinetics, efficacy of HA121-28 were assessed in advanced solid tumors (phase 1, ClinicalTrials.gov NCT03994484) RET fusion-positive non-small-cell lung cancer (RET-TKI naive NSCLC, phase 2, NCT05117658). was administered orally doses range from 25 to 800 mg under the 21-day on/7-day off scheme for 28-day cycle 1 trial. recommended dose identified (450 mg) patients 2. primary endpoints maximum tolerated (MTD) objective response rate (ORR) 162 enrolled 48 A total 600 once daily set as MTD. Across 100–800 mg, exposure increased dose-dependent manner. Consistent between both trials, diarrhea, rash, prolonged QTc interval, most reported treatment-emergent adverse events. 40.0% 1) 62.5% 2) experienced grade ≥3 treatment-related events, respectively. overall ORR 26.8% median progression-free survival (PFS) 5.5 months among 97 NSCLC with fusion receiving at ≥450 daily. showed encouraging its toxicity tolerable patients. Nevertheless, cardiotoxicity is notable concern that warrants careful attention.

Language: Английский

---

Treatment of RET/ALK comutated advanced lung large cell neuroendocrine carcinoma: a case report and literature review

Anti-Cancer Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

The prognosis of advanced lung large-cell neuroendocrine carcinoma is poor, and the efficacy targeted therapy still being explored. A case RET fusion mutation combined with ALK rearrangement positive complex large cell was reported. patient developed intrapulmonary bone metastases 8 months after chemotherapy cancer surgery, mutations were detected by genetic testing, intracranial progression occurred 1 year pilatinib applied. comutation pulmonary 2 application aletinib, treated he progressed again in 9 months. We point out that patients gene can benefit from therapy, when drug resistance accompanied comutation, treatment aletinib side effect slight. At same time, we further explore mechanism cancer.

Language: Английский

---

Cancers du poumon avec addictions rares : RET, ROS-1, MET, HER2 et BRAF

Bulletin du Cancer, Journal Year: 2025, Volume and Issue: 112(3), P. 3S117 - 3S126

Published: March 1, 2025

Language: Английский

---

Oncogenic Fusions in NSCLC: From Mechanisms to Clinical Applications

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3802 - 3802

Published: April 17, 2025

Non-small cell lung cancer (NSCLC) is operated commonly by diverse genetic alterations, and oncogenic fusions represent a significant therapeutic role. Common include ALK, ROS1, RET, NTRK, signaling pathways in tumorigenesis. Recent advances investigating tumor molecular biology underlying fusions, including chromosomal rearrangements, highlighting their role as drivers. The development of targeted therapies, such tyrosine kinase inhibitors (TKIs), has impacted most patients’ NSCLC treatment. Despite the greater profiles, remarkable efficiency tolerable side effects compared to traditional chemotherapy, challenges, acquired mutations, lead more ongoing research-optimized future therapies.

Language: Английский

---

RET fusion driven (RETfus+) non-small cell lung cancer: a comprehensive genomic profiling study with histologic correlation

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: May 16, 2025

Background Fusion of the RET gene resulting in clinically significant Genomic Alteration (GA) occur 1-2% NSCLC United States and has emerged as a major target for inhibitors which are first line treatment options Stage 4 setting. fusions have also been well-described acquired resistance mutations cases EGFR -driven treated with anti- tyrosine kinase including erlotinib osimertinib. The aim this study was to determine whether fusion positive ( RETfus+ ) represents unique histologic subtype disease genomic profile. Methods We selected 503 72,596 (0.7%) total that were reported from Foundation One database. centrally evaluated predominant histology underwent hybrid capture based CGP evaluate diverse GA. Cases excluded. PD-L1 expression determined by Immunohistochemistry (IHC) (Dako 22C3) Tumor Proportion Score (TPS) ≥50% = high expression. For statistical comparisons, false discovery rate corrected using Benjamini/Hochberg adjustment. Results Potentially targetable GAs found less frequently group included BRCA1, BRAF, FGF12, FGFR1, KEAP1, KMT2D, KRAS, MDM2, MET, NF1, NSD3, PIK3CA, RB1 , AND TP53 . presence HRD, APOBEC Tobacco signatures lower frequencies RETFus+ cases. SETD2 only GA be higher group. While markers predictive checkpoint therapy response TMB level more frequent RETfus- cases, samples. Surgical pathology analysis revealed grade solid non-acinar pattern at 32% most subtype. Conclusions features signature can further impact selection. With recent expanded approval specific targeting (selpercatinib Pralsetinib) pan-cancer setting, RETfusion+ genomic/biomarker status appears warranted.

Language: Английский

---