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selpercatinib

✓ Approved

Loxo Oncology · NTRK1 · 辅助诊断

什么是 selpercatinib？

selpercatinib 是一种辅助诊断，由Loxo Oncology研发。该药已获批，用于治疗相关适应症，给药途径：Others。

药物档案

公司Loxo Oncology
药物类别辅助诊断
分子靶点NTRK1
给药途径Others
状态Approved
来源： ClinicalTrials.gov, Loxo Oncology

作用机制

分子靶点

selpercatinib 作用于 1 个分子靶点：

NTRK1neurotrophic receptor tyrosine kinase 1 (TRK1, TRK)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

selpercatinib 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Uterine cancer✓ Approved

相关研究文献

PubMedAntibiotics (Basel, Switzerland)2026-07-27

Evolution and Antimicrobial Resistance Profiles of Klebsiella spp. Infections in Companion Animals in the Iberian Peninsula.

Jiménez-Serrano María M, Vidal Anna A, Duran Inma I, Seminati Chiara C et al.

Antimicrobial resistance (AMR) in companion animals is an increasing concern within the One Health framework, particularly regarding opportunistic pathogens such as Klebsiella spp. This retrospective study evaluated the epidemiology, antimicrobial susceptibility profiles, and temporal resistance trends of Klebsiella spp. infections in dogs and cats across the Iberian Peninsula. A total of 809 clinical isolates collected between 2016 and 2024 and submitted to a private diagnostic laboratory in Barcelona were analysed. Klebsiella pneumoniae was the predominant species (70%), more frequently identified in cats (76%) than in dogs (68%). Dermatological and respiratory samples exhibited the highest prevalence of multidrug-resistant (MDR) isolates. Overall MDR prevalence was high, particularly in cats (51.1%; 95% CI 41.1-60.9%) compared with dogs (38.4%; 95% CI 34.1-42.8%) although it was not statistically significant. K. pneumoniae generally exhibited higher resistance rates than K. oxytoca, particularly to amoxicillin/clavulanic acid, first-/second-generation cephalosporins, third-/fourth-generation cephalosporins (3/4th GC), fluoroquinolones, and tetracyclines. In both bacterial species, resistance rates were consistently higher among feline isolates. In contrast, aminoglycosides and phenicols retained high activity against most isolates. Temporal analysis revealed a significant increasing resistance trend to amoxicillin/clavulanic acid, which is particularly concerning given the widespread use of this antimicrobial as a first-line treatment in small animal practice. However, resistance trend to aminoglycosides showed a significant decline. No significant temporal changes were detected for 3/4th GC and fluoroquinolones, suggesting the persistence of resistant populations within companion animals. Resistance to aminoglycosides and phenicols remained comparatively low in this study. Whereas critically important category B antimicrobials, such as 3/4th GC and fluoroquinolones, exhibited low to moderate effectiveness, raising concerns about their empirical use. These findings highlight the substantial AMR and MDR burden of K. pneumoniae in companion animals in the Iberian Peninsula and reinforce the need for prudent antimicrobial use, routine susceptibility testing, and integrated One Health surveillance strategies.

PMID 42505641
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PubMedAntibiotics (Basel, Switzerland)2026-07-27

First Report of a blaOXA-484-Harbouring Escherichia coli ST167 Isolated from the Urine Sample of a Dog of Italian Origin.

Biggel Michael M, Nüesch-Inderbinen Magdalena M, Schmitt Sarah S, Schneeberger Marianne M et al.

Antimicrobial resistance (AMR) is a global threat to both human and animal health. Carbapenems are last-resort antimicrobials used to treat severe infections with multidrug-resistant Gram-negative nosocomial pathogens in humans. Therefore, the dissemination of carbapenemase-producing Enterobacterales (CPE) has emerged as a major concern worldwide. Although carbapenems are not routinely used in veterinary medicine, CPE, including OXA-48-like-producing Escherichia coli, are increasingly being reported in companion animals. We document the first report of E. coli-harbouring blaOXA-484 isolated from a urine sample from a dog with a history of chronic thoracolumbar myelopathy. Using a combined Oxford Nanopore (ONT) long-reads and Illumina short-reads sequencing approach, the isolate was characterized and an IncF plasmid containing blaOXA-484 was reconstructed. The isolate belonged to sequence type (ST)167, which is an emerging high-risk clone frequently reported among human clinical isolates. The blaOXA-484 gene was harboured in a composite transposon bracketed by IS26 identical to that of blaOXA-484 carried on an IncX plasmid pOXA-484-JS316 from a human clinical E. coli ST410 from Germany. The isolation of the epidemic clone ST167 harbouring blaOXA-484 from a canine infection raises the hypothesis of a transmission event between humans and companion animals.

PMID 42505615
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PubMedThoracic cancer2026-07-27

Sequential EGFR T790M, MET c.3010C>G-Associated Exon 14 Alteration, and RET-CCDC6 Fusion in EGFR-Mutant NSCLC: A Case Report.

Zhu Yan Y, Wang Chan C, Hu Nan-Lin NL, Wang Dan-He DH et al.

Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell lung cancer (NSCLC) is heterogeneous, and serial re-biopsy may uncover actionable mechanisms. We report a 55-year-old man with stage IVB lung adenocarcinoma harboring EGFR L858R and TP53 R282W. First-line icotinib produced a partial response (PR) with progression-free survival (PFS) of 7 months. Rebiopsy at progression identified acquired EGFR T790M together with a MET c.3010C>G exon 14-related alteration. Almonertinib induced a second PR lasting 7 months. After renewed progression, almonertinib plus savolitinib achieved another PR for 8 months, supporting MET-dependent bypass resistance. Biopsy of a newly progressive iliac metastasis then showed emergence of RET-CCDC6 fusion, whereas T790M and the MET alteration were no longer detected. Because selective RET inhibition was initially unaffordable, the patient received pemetrexed-carboplatin plus continued almonertinib, followed by selpercatinib plus almonertinib. Local radiotherapy to oligoprogressive bone and lung lesions prolonged benefit from systemic therapy. At the latest follow-up in January 2026, the patient remained alive nearly 50 months after diagnosis. This case illustrates clonal evolution under treatment pressure and highlights three practical lessons: repeat molecular testing at each clinically meaningful progression, matched combination targeted therapy for actionable bypass alterations, and local ablative radiotherapy for oligoprogression.

PMID 42503459
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PubMedJournal of clinical microbiology2026-07-27

Veterinary-specific breakpoints for ceftiofur applicable to canine Escherichia coli.

Dang Xukun X, Chen Siyu S, Lyu Hening H, Zou Zhiyu Z et al.

Ceftiofur is a third-generation cephalosporin approved for veterinary applications and is used to treat Escherichia coli infections in dogs, particularly urinary tract infections (UTIs), in countries including China. Despite this use, there are no approved breakpoints for interpretation of ceftiofur susceptibility testing results. This absence limits the guidance that veterinarians need to effectively prescribe ceftiofur in dogs. It also limits the analysis of data from resistance monitoring and surveillance programs. This study aimed to establish ceftiofur interpretive categories and breakpoints that can be used to assess antimicrobial susceptibility testing results for canine E. coli isolates. Our methods included a definition of the wild-type cutoff (COWT) based on resistance phenotypes from two sources, deriving the pharmacokinetics/pharmacodynamics (PK-PD) cutoff (COPD) through PK-PD analyses and Monte Carlo simulations and determining the clinical cutoff (COCL) from a trial in dogs. Minimal inhibitory concentration (MIC) data were collected from China and the European database (European Committee on Antimicrobial Susceptibility Testing [EUCAST]). COWT was determined as 1 μg/mL. The COPD was 0.25 μg/mL. Through a canine cystitis trial, a COCL of 2 μg/mL was determined. Based on these findings and Clinical and Laboratory Standards Institute (CLSI)-recommended methods, we propose urinary tract infection-specific MIC breakpoints of ≤1 µg/mL (susceptible), 2 μg/mL (intermediate), and ≥4 µg/mL (resistant) and corresponding disk diffusion zone diameter breakpoints, determined by the error rate-bounded (ERB) method, of ≥23 mm (susceptible), 20-22 mm (intermediate), and ≤19 mm (resistant). The systemic breakpoints (non-urine) were determined to be ≤0.125 µg/mL (susceptible), 0.25 μg/mL (intermediate), and ≥0.5 µg/mL (resistant).IMPORTANCECeftiofur can be legally used, but laboratories and veterinarians lack canine-specific breakpoints to determine whether an isolate is susceptible or resistant. Without such criteria, test results can be inconsistent, treatment choices uncertain, and early signs of emerging resistance overlooked. This study fills that gap by defining evidence-based, canine-specific breakpoints for ceftiofur, particularly for urinary tract infections (UTIs). Adoption of these breakpoints will allow more consistent reporting by diagnostic laboratories, improve therapeutic decision-making for veterinarians, and provide a reliable basis for resistance surveillance. These advances strengthen the One-Health antimicrobial stewardship and help preserve the effectiveness of important antimicrobials for companion animals and the wider community.

PMID 42506934
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PubMedCurrent oncology (Toronto, Ont.)2026-07-27

Controversies in the Management of AML in Older Patients: A Canadian Perspective.

Schuh Andre C AC, Brandwein Joseph J, Elsawy Mahmoud M, Sanford David D et al.

In the companion article in this issue of Current Oncology, 'Management of AML in Older Patients: An Updated Canadian Consensus', the authors have presented the third iteration of Canadian consensus guidelines on AML treatment in the elderly. While many aspects of AML treatment in the elderly have become better defined, some old questions remain and new questions and controversies have arisen. Here, we address three topics on which there is, at this time, no universal consensus. The first is the development and features of new risk-stratification systems specifically aimed at older, less-intensively treated patients. Several different systems now exist in parallel, potentially causing confusion amongst clinicians. The second topic is good-prognosis AML subtypes (IDH1- and NPM1-mutated AML). In the Canadian context, IDH1-mutated AML is of particular interest due to the new availability of ivosidenib in Canada. The third topic is adverse-risk AML subtypes (FLT3- and TP53-mutated AML). FLT3-mutated AML remains problematic, although it is anticipated that new drug approvals and measurable residual disease-based treatment approaches may alleviate this, at least in part. And in particular, TP53-mutated AML remains a major problem. Ongoing clinical trial enrollment is essential.

PMID 42505233
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PubMedAntibiotics (Basel, Switzerland)2026-07-27

Skin Infection Pathogenicity Associated with a Canine Microbiome Resident: Polygenic Architecture of Virulence Factors in Staphylococcus pseudintermedius.

Javaid Aqib A, Tabassum Nazia N, Karthikeyan Abirami A, Kim Tae-Hee TH et al.

Staphylococcus pseudintermedius is a common opportunistic pathogen in companion animals and a leading cause of skin and soft tissue infections (SSTIs). Despite its clinical relevance, the genomic determinants underlying pathogenicity and the transition from commensal carriage to invasive infection remain poorly understood. This study aimed to identify the genomic determinants of SSTI pathogenic potential in S. pseudintermedius and to determine whether pathogenicity is driven by single, major-effect virulence genes or by polygenic genome-wide genetic architecture. Using accessory gene-based and unitig-based genome-wide association studies (GWASs), employing a linear mixed model, across a genetically diverse collection of S. pseudintermedius isolates spanning multiple phylogenetic clades, we found that disease and carriage isolates showed no phylogenetic clustering. SSTI pathogenicity exhibited high narrow-sense heritability. Surface-associated LPXTG-anchored proteins, particularly spsF, harbored the strongest associations, with additional signals in iron metabolism (narH, sufB) and oxidative stress tolerance (ahpC). Random Forest classification validated GWAS signals. SSTI pathogenicity in S. pseudintermedius reflects a polygenic architecture driven by cumulative variation across surface-associated, metabolic, and stress-response loci, shifting focus from single virulence genes to genome-wide genetic variation.

PMID 42505675
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