Rare molecular subtypes of lung cancer

Harada, Guilherme; Yang, Soo‐Ryum; Cocco, Emiliano; Drilon, Alexander

doi:10.1038/s41571-023-00733-6

Cited by 43 publications

(36 citation statements)

References 190 publications

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“…Unlike EGFR-mutated or ALK fusion NSCLC, MET exon 14 mutations are seen in older patients 41 and in various histologies, including adenocarcinoma (2%), sarcomatoid carcinoma (13%), adenosquamous carcinoma (6%), and histologic subtypes of NSCLC. 42,43 Detection Methods…”

Section: Epidemiology and Clinical Characteristicsmentioning

confidence: 99%

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Path Less Traveled: Targeting Rare Driver Oncogenes in Non–Small-Cell Lung Cancer

Lim,

Lee,

Oya

et al. 2024

JCO Oncol Pract

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Over the past decade, tremendous efforts have been made in the development of targeted agents in non–small-cell lung cancer (NSCLC) with nonsquamous histology. Pivotal studies have used next-generation sequencing to select the patient population harboring oncogenic driver alterations that are targetable with targeted therapies. As treatment paradigm rapidly evolves for patients with rare oncogene-driven NSCLC, updated comprehensive overview of diagnostic approach and treatment options is paramount in clinical settings. In this review article, we discuss the epidemiology, molecular testing, and landmark clinical trials addressing the targeted agents for ROS1 rearrangement, METex14 skipping mutation, EGFR exon 20 insertion, KRAS G12C mutation, HER2 mutation, RET fusion, NTRK fusion, and BRAF mutations.

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Section: Epidemiology and Clinical Characteristicsmentioning

confidence: 99%

“…84 NGS of DNA or RNA of tumor samples increases the sensitivity of detection of RET fusion partners by including less common and novel gene fusions. 42 At progression, circulating cell-free DNA (cfDNA) has been used to identify the resistance mechanism and co-occurring mutations in RET -altered NSCLC for exploratory purposes. 86–88…”

Section: Ret Fusionmentioning

confidence: 99%

Path Less Traveled: Targeting Rare Driver Oncogenes in Non–Small-Cell Lung Cancer

Lim,

Lee,

Oya

et al. 2024

JCO Oncol Pract

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“…MAP2K1 (MEK1) is a kinase and a key constituent of the mitogen-activated protein kinase (MAPK) pathway which drives cellular proliferation and survival [1][2][3] . It is a recurrently mutated oncogene in human cancers, particularly Langerhans cell histiocytosis, melanoma, colorectal cancer, and non-small cell lung adenocarcinoma [4][5][6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

Clinical activity of Mitogen-Activated Protein Kinase (MAPK) inhibitors in patients with MAP2K1 (MEK1)-mutated metastatic cancers

Dankner,

Rousselle,

Petrecca

et al. 2024

Preprint

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PURPOSEMAP2K1/MEK1 mutations are potentially actionable drivers in cancer. MAP2K1 mutations have been functionally classified into three groups according to their dependency on upstream RAS/RAF signaling. However, the clinical efficacy of MAPK pathway inhibitors (MAPKi) for MAP2K1 mutant tumors is not well defined. We sought to characterize the genomic and clinical landscape of MAP2K1 mutant tumors to evaluate the relationship between MAP2K1 mutation Class and clinical activity of MAPKi.METHODSWe interrogated AACR GENIE (v13) to analyze solid tumors with MAP2K1 mutations. We performed a systematic review and meta-analysis of published reports of patients with MAP2K1 mutant cancers treated with MAPKi according to PRISMA guidelines. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall response rate (ORR), duration of response (DOR), and overall survival (OS).RESULTSIn the AACR GENIE dataset, Class 2 MAP2K1 mutations (63%) were more prevalent than Class 1 (24%) and Class 3 (13%) mutations (P<0.0001). Co-occurring MAPK pathway activating mutations were more likely to occur in Class 1 versus Class 2 or 3 MAP2K1 mutant tumors (P<0.0001). Our systematic meta-analysis of the literature identified 46 patients with MAP2K1 mutant tumors who received MAPKi. In these patients, ORR was 28% and median PFS was 3.9 months. ORR did not differ according to MAP2K1 mutation class or cancer type. However, patients with Class 2 mutations experienced longer PFS (5.0 months) and DOR (23.8 months) compared to patients with Class 1, 3 or unclassified MAP2K1 mutations (PFS 3.5 months, P=0.04; DOR 4.2 months, P=0.02).CONCLUSIONPatients with Class 2 MAP2K1 mutations represent a novel subgroup that may derive benefit from MAPKi. Prospective clinical studies with novel MAPKi regimens are warranted in these patients.Highlights- A meta-analysis describing clinical outcomes with MAPK targeted therapy in MAP2K1 mutant tumors.- Clinical validation of MAP2K1 mutation Class as a predictive biomarker.- Class 2 MAP2K1 mutations are sensitive to MEK-inhibitor containing regimens.Graphical Abstract

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“…Furthermore, NGS is a powerful tool for diagnosing and treating NSCLC, as it can be used to monitor the response to treatment and detect resistance development 10 . The use of NGS and the treatment of NSCLC are still evolving; however, NGS can potentially revolutionize the way that this cancer is managed 11 . NGS requires smaller samples than sequential methods of individual genetic testing 12–16 .…”

Section: Introductionmentioning

confidence: 99%

Comparison of the slow‐pull and aspiration methods of endobronchial ultrasound‐guided transbronchial needle aspiration for next‐generation sequencing‐compatible tissue collection in non‐small cell lung cancer

Kajita,

Teranishi,

Sawazumi

et al. 2023

Cancer Medicine

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BackgroundPersonalized treatment for non‐small cell lung cancer (NSCLC) has advanced rapidly, and elucidating the genetic changes that trigger this disease is crucial for appropriate treatment selection. Both slow‐pull and aspiration methods of endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) are accepted methods for collecting samples suitable for next‐generation sequencing (NGS) to examine driver gene mutations and translocations in NSCLC. Here, we aimed to determine which of these two methods is superior for obtaining higher‐quality samples from patients with NSCLC.MethodsSeventy‐one patients diagnosed with NSCLC via EBUS‐TBNA using the slow‐pull or aspiration (20‐mL negative pressure) methods between July 2019 and September 2022 were included. A total of 203 tissue samples from the 71 patients were fixed in formalin, embedded in paraffin, and mounted on slides. The presence of tissue cores, degree of blood contamination, and number of tumor cells were compared between the groups. The success rate of NGS, using Oncomine Dx Target Test Multi‐CDx, was also compared between the groups.ResultsThe slow‐pull method was associated with a higher yield of tissue cores, lower degree of blood contamination, and higher number of tumor cells than the aspiration method. The success rate of the NGS was also significantly higher for the slow‐pull group (95%) than for the aspiration group (68%).ConclusionOverall, these findings suggest that the slow‐pull method is a superior technique for EBUS‐TBNA to obtain high‐quality tissue samples for NGS. The slow‐pull method may contribute to the identification of driver gene mutations and translocations and facilitate personalized treatment of NSCLC.

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Rare molecular subtypes of lung cancer

Cited by 43 publications

References 190 publications

Path Less Traveled: Targeting Rare Driver Oncogenes in Non–Small-Cell Lung Cancer

Path Less Traveled: Targeting Rare Driver Oncogenes in Non–Small-Cell Lung Cancer

Clinical activity of Mitogen-Activated Protein Kinase (MAPK) inhibitors in patients with MAP2K1 (MEK1)-mutated metastatic cancers

Comparison of the slow‐pull and aspiration methods of endobronchial ultrasound‐guided transbronchial needle aspiration for next‐generation sequencing‐compatible tissue collection in non‐small cell lung cancer

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