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pasireotide (Signifor LAR / pasireotide, LAR / pasireotide LAR)

✓ Approved

Novartis AG · SSTR1 · 小分子

什么是 pasireotide？

pasireotide 是一种小分子，由Novartis AG研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Intramuscular (IM) Injection、Subcutaneous Injection。

药物档案

商品名Signifor LAR, pasireotide, LAR, pasireotide LAR
公司Novartis AG
药物类别小分子, 多肽类
分子靶点SSTR1, SSTR2, SSTR3, SSTR5
给药途径Injectable (Others), Intramuscular (IM) Injection, Subcutaneous Injection
状态Approved
来源： ClinicalTrials.gov, Novartis AG

作用机制

分子靶点

pasireotide 作用于 4 个分子靶点：

SSTR1somatostatin receptor 1 (SS-1-R, SS1-R)
SSTR2somatostatin receptor 2 (SST2)
SSTR3somatostatin receptor 3 (SST3, SS3R)
SSTR5somatostatin receptor 5 (SST5, SS-5-R)
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

pasireotide 针对 11 个适应症，涉及 2 个治疗领域。

治疗领域疾病/病症分期
Endocrine disordersAcromegaly✓ Approved
Endocrine disordersPituitary-dependent Cushing's syndrome✓ Approved
Endocrine disordersCarcinoid syndromePhase III
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Colon cancer recurrentPhase III
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Pituitary tumour benignPhase II

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相关研究文献

PubMedShoulder & elbow2026-06-12

Temporal trends and estimated lifetime attributable radiation risk of preoperative planning computed tomography for primary shoulder arthroplasty.

Kalva Swara R SR, Fucich Dario D, Perry Arthur J AJ, Lezak Bradley B et al.

Advantages of preoperative planning computed tomography (CT) scans for shoulder arthroplasty (SA) are known; however, risks of ionizing radiation exposure remain unknown. We retrospectively reviewed institutional trends in utilization and estimated radiation risk of preoperative planning CT scans obtained for SA. From 2016 to 2024, the annual percent incidence of SA patients that received a preoperative planning CT was determined. The National Academy of Sciences Biological Effects of Ionizing Radiation VII report on lifetime attributable risk (LAR) cancer incidences and received radiation dose were utilized to estimate patient-level LAR projections for 100 patients stratified by sex, age, and cancer type. From 2016 to 2024, utilization of preoperative planning CT increased linearly (R2 = 0.78) from 53% to 66% of all SA patients. For all solid cancers, LAR (per 100,000 people) decreased as patient age increased, ranging from 73.1 to 9.6 for females and 40.7 to 31.4 for males (from the 50-59-year-old group to the 80-89 group). In the 60-69-year-old and 70-79-year-old groups, estimated thyroid and lung LARs were significantly higher in women. Utilization of preoperative shoulder CT scans is increasing. Preoperative shoulder CT may be associated with a small but quantifiable projected cancer risk most pronounced in younger women.

PMID 42282944
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PubMedJournal of clinical medicine2026-06-12

Early Postoperative Predictors of 30-Day Mortality After Pediatric Liver Transplantation: A Trajectory-Based Analysis.

Bingol Ibrahim I, Yilmaz Tonguc Utku TU, Umur Ozge O, Sık Guntulu G et al.

Background/Objectives: Early mortality after pediatric liver transplantation remains a clinical challenge, yet few studies have specifically addressed 30-day outcomes. Conventional pretransplant scores such as the age-appropriate MELD/PELD score were not designed for post-transplant risk prediction. We aimed to evaluate whether dynamic postoperative biomarker trajectories and novel composite ratios can identify high-risk patients. Methods: This single-center retrospective cohort study included 140 consecutive pediatric patients (<18 years) who underwent primary liver transplantation between 2015 and 2023. Patients were classified as deceased (≤30 days, n = 11) or survivors (>30 days, n = 129). PRISM-III, PELOD-2, and age-appropriate MELD/PELD scores were evaluated. Serial laboratory parameters were collected at pretransplant and at 0, 24, and 72 h. Delta (Δ) values and composite ratios-including lactate clearance, lactate-to-albumin ratio (LAR), INR×lactate product, platelet ratio, and fibrinogen/INR-were calculated. Penalized logistic regression (Firth method) was used for multivariate analysis. Internal validation was performed using bootstrap resampling (1000 iterations) and leave-one-out cross-validation (LOO-CV). Because two of the three components of the multivariable model (ΔINR, ΔALT) were derived from 72-h values, the model is best understood as a 72-h landmark risk model rather than as an immediate post-transplant early-warning tool. Results: The 30-day mortality rate was 7.9% (11/140), with central nervous system complications as the leading cause (36.4%). PRISM-III demonstrated excellent discrimination (AUROC 0.957; cut-off ≥ 14); the age-appropriate MELD/PELD score, a pretransplant tool not designed for post-transplant prediction, showed near-chance performance (AUROC 0.513; p = 0.576). A distinctive biomarker crossover pattern was observed: non-survivors had paradoxically lower pretransplant INR, ALT, and LAR values, but trajectories diverged sharply by 24 h. The INR×lactate product achieved an AUROC of 0.981 at 72 h. LAR at 24 h achieved 0.909, and lactate clearance at 0 → 72 h achieved 0.783. Postoperative hypernatremia emerged as a strong predictor (AUROC 0.884). In multivariate analysis, PRISM-III (OR 4.00), ΔINR (OR 3.28), and ΔALT (OR 3.46) were independent predictors (apparent AUROC 0.989). Internal validation confirmed model stability: bootstrap-corrected AUROC was 0.978; LOO-CV AUROC was 0.957 (sensitivity 90.9%, specificity 96.9%). Conclusions: Dynamic postoperative factors-rather than pretransplant disease severity-appeared more strongly associated with 30-day mortality after pediatric liver transplantation in this single-center exploratory analysis. The INR×lactate product, a novel two-variable composite, showed very high apparent discrimination (AUROC 0.981) and is proposed as a hypothesis-generating candidate marker requiring prospective external validation before any clinical use. The combined PRISM-III + ΔINR + ΔALT model (best understood as a 72-h landmark risk model, since two of its three components are defined at 72 h postoperatively) demonstrated robust internal validation performance (LOO-CV AUROC 0.957); however, given the small number of events (n = 11) and the absence of external validation, the model should be regarded as exploratory.

PMID 42279245
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PubMedInternational journal of molecular sciences2026-06-12

Beyond Molecular Classification in Metastatic Triple-Negative Breast Cancer: Toward Subtype-Guided Precision Oncology.

Pekarek Leonel L, García-Montero Cielo C, Casanova-Martin Carlos C, Ortega Miguel A MA et al.

Metastatic triple-negative breast cancer (mTNBC) remains one of the most challenging therapeutic settings in oncology. Although it has traditionally been defined by the absence of hormone receptor expression-estrogen receptor (ER) and progesterone receptor (PR)-and HER2 amplification or overexpression, this simplified definition fails to capture the biological complexity that drives its marked clinical heterogeneity, therapeutic resistance, and prognostic variability. Over the past decade, multiple studies have challenged the notion of TNBC as a single disease entity, identifying distinct molecular subtypes, including Basal-like 1 (BL1), Basal-like 2 (BL2), Mesenchymal (M), Mesenchymal Stem-like (MSL), Immunomodulatory (IM), and Luminal Androgen Receptor (LAR), each characterized by specific biological programs and therapeutic vulnerabilities. In parallel, clinically oriented systems such as the Fudan classification have enabled the prospective evaluation of subtype-guided therapeutic strategies in metastatic disease, as illustrated by the FUTURE and FUTURE-SUPER trials. In this review, we examine the molecular classification and clinical behavior of mTNBC subtypes, integrating genomic, transcriptomic, epigenetic, immunologic, stromal, and biomechanical dimensions of tumor heterogeneity. We also discuss emerging tools, including single-cell RNA sequencing, spatial transcriptomics, circulating tumor DNA analysis, long non-coding RNA profiling, and surrogate immunohistochemistry-based classifiers, as well as their potential role in refining patient stratification. From a therapeutic perspective, we review subtype-guided strategies involving chemotherapy, platinum agents, PARP inhibitors, immunotherapy, antiandrogen therapy, PI3K/AKT/mTOR pathway inhibition, antiangiogenic approaches, and antibody-drug conjugates. Redefining mTNBC through biologically driven stratification represents a rational strategy to optimize treatment selection, support clinical trial design, and accelerate the development of precision oncology approaches. However, clinical implementation requires greater methodological standardization, validated predictive biomarkers, accessible diagnostic platforms, and dynamic monitoring strategies capable of capturing subtype evolution under therapeutic pressure. TNBC should therefore not be regarded as a single disease, but as a spectrum of biologically distinct and clinically evolving entities whose integrated characterization may be essential to improving outcomes in this historically poor-prognosis population.

PMID 42278564
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PubMedThe international journal of lower extremity wounds2026-06-11

Lactate-to-Albumin Ratio for Predicting Intensive Care Unit Admission in Patients with Diabetic Foot Infection.

Yusufoglu Kaan K, Yonga Omer O

BackgroundEarly identification of diabetic foot infection (DFI) patients at risk for clinical deterioration is critical for timely intervention. Serum lactate reflects tissue hypoperfusion, whereas hypoalbuminemia indicates systemic inflammation and poor nutritional status. The aim of this study is to evaluate the ability of the lactate-to-albumin ratio (LAR) to predict ICU admission in patients with DFI.MethodsThis retrospective study was conducted in the emergency department of a tertiary care center between 01.01.2022 and 01.01.2025. Adult patients (≥18 years) with confirmed DFI were included. DFI diagnosis was established in accordance with IWGDF/IDSA 2023 criteria.1 Patients with chronic liver failure, nephrotic syndrome, pregnancy, or incomplete records were excluded. LAR was calculated as lactate (mmol/L) divided by albumin (g/dL). The primary outcome was ICU admission, defined as direct admission from the emergency department based on clinical severity assessment. ROC analyses assessed the predictive performance of LAR compared with lactate and albumin. Multivariable logistic regression identified independent predictors of ICU admission.ResultsAmong 494 patients (median age, 64 years; 40.3% female), 91 (18.4%) required ICU admission. ICU patients had higher lactate (2.5 vs 1.8 mmol/L, P < .001), lower albumin (3.2 vs 3.4 g/dL, P < .001), and higher LAR (0.8 vs 0.5, P < .001). LAR demonstrated the best discrimination for ICU admission (AUC, 0.717; 95% CI, 0.658-0.777), outperforming albumin (AUC, 0.626; P = .009) and similar to lactate (AUC, 0.702; P = .134). A cut-off of ≥0.73 yielded 57.1% sensitivity and 78.2% specificity. LAR (OR, 1.36; 95% CI, 1.16-1.58; P < .001), older age, lower mean arterial pressure, and lower ankle-brachial index were independent predictors of ICU admission.ConclusionsThe lactate-to-albumin ratio is a simple, cost-effective biomarker that independently predicts ICU admission in DFI patients and may aid early risk stratification. Although LAR did not demonstrate statistically superior discrimination over lactate alone, it integrates systemic metabolic stress with the host's inflammatory and nutritional reserve, offering a composite measure of physiological vulnerability in this high-risk population.

PMID 42273767
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PubMedEndocrine journal2026-06-11

Recurrent Cushing's disease due to postoperative seeding of tumor cells in the sphenoid sinus: a case report with review of the literature.

Matsuda Tatsuma T, Fukuhara Noriaki N, Tosaka Masahiko M, Horiguchi Kentaro K et al.

Recurrent Cushing's disease is most commonly caused by residual or newly developed pituitary neuroendocrine tumor (PitNET) tissue within the sellar region. Extrasellar recurrence due to postoperative tumor cell seeding is exceedingly rare. We report the unique case of a 30-year-old woman who achieved endocrine remission after gross total resection of an ACTH-secreting PitNET but later developed biochemical and clinical recurrence without radiological evidence of a sellar lesion. Despite long-term medical therapy including cabergoline, metyrapone, and pasireotide, the hypercortisolism gradually progressed. Nearly 10 years after the initial surgery, a reoperation was performed to explore the occult tumor. Intraoperatively, a small soft tumor attached to the posterior surface of the anterior wall of the sphenoid sinus was discovered. Histopathological examination confirmed the presence of a recurrent corticotrophic PitNET. A retrospective review of CT, MRI, and octreotide scintigraphy revealed a subtle lesion that had previously been overlooked. Complete resection resulted in an immediate endocrine remission. This case demonstrates that recurrent Cushing's disease may, although rarely, arise from the implantation of tumor cells that drop into the sphenoid sinus during transsphenoidal surgery. Awareness of this mechanism is crucial for evaluating MRI-negative recurrences. Careful inspection of the sphenoid sinus and meticulous irrigation during surgery may help prevent iatrogenic seeding and improve long-term outcomes.

PMID 42270362
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PubMedCureus2026-06-11

Pancreatic Neuroendocrine Tumor in Lynch Syndrome: Expanding the Tumor Spectrum of Mismatch Repair Deficiency.

Mudupula Vemula Sai Sushrutha SS, Sanka Soumith S, Natarajan Varun V, Varghese Merryl T MT et al.

Lynch syndrome is an autosomal dominant hereditary cancer syndrome caused by germline mutations in DNA mismatch repair genes. Currently, Lynch syndrome has well-established associations with colorectal and endometrial cancers. However, a definitive association between Lynch syndrome and pancreatic neuroendocrine tumors (P-NETs) remains unestablished. Herein, we report the case of a 38-year-old male with a maternal family history of Lynch syndrome who presented with hypoglycemia, abdominal pain, and diarrhea. Imaging revealed a 5.6 cm pancreatic tail mass with hepatic, lymph node, and osseous metastases. Synchronous sigmoid adenocarcinoma was identified during admission. Germline testing confirmed a pathogenic MLH1 mutation, and liver biopsy of the P-NET demonstrated loss of MLH1 and PMS2 expression. The patient was treated with capecitabine and temozolomide (CAPTEM) chemotherapy, pembrolizumab, long-acting repeatable octreotide (octreotide LAR), and diazoxide for hypoglycemia management. Disease progression with spinal epidural extension necessitated palliative radiation and intravenous immunoglobulin for severe thrombocytopenia. This case highlights the expanding phenotypic spectrum of Lynch syndrome and suggests that P-NETs may represent a rare but clinically significant manifestation. Early recognition of this association supports comprehensive genetic testing, enables the use of precision immunotherapy, and underscores the need for expanded surveillance strategies in patients with atypical tumor profiles.

PMID 42273517
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