Neuroendocrine Tumor

P=N/A, N=20, Recruiting, Nanjing First Hospital, Nanjing Medical University

P1/2, N=60, Not yet recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd

H1048-ER cells showed cross-resistance to cisplatin but were sensitive to doxorubicin and temozolomide. Our study provides novel insights into etoposide resistance in SCLC and affords the potential treatment options after etoposide resistance.

This case adds to the knowledge of an extremely rare presentation of breast metastases from an extramammary malignancy, cervical SCNEC. It is important to differentiate between primary breast cancer metastasis and metastasis to the breast from other cancers because of the different therapeutic options.

This highlights its promise as an immune checkpoint biomarker and therapeutic target. The collective data from this review provide insights for future research endeavors in HHLA2-associated oncology.

P2, N=140, Suspended, M.D. Anderson Cancer Center | Trial completion date: Apr 2025 --> Apr 2026 | Trial primary completion date: Apr 2025 --> Apr 2026

P2, N=84, Completed, Gustave Roussy, Cancer Campus, Grand Paris | Recruiting --> Completed

discover that small cell lung cancer and neuroendocrine prostate cancer highly express a circular RNA known as circRMST. They show that circRMST is necessary for these neuroendocrine cancers to promote their ASCL1-positive neuroendocrine phenotype through binding lineage transcription factors that promote ASCL1 expression.

Mechanistically, circRMST physically interacts with lineage transcription factors NKX2-1 and SOX2. Loss of circRMST induces NKX2-1 protein degradation through autophagy-lysosomal pathway and alters the genomic binding of SOX2, collectively leading to the loss of ASCL1 transcription.

Everolimus, an mTOR inhibitor, was shown to counteract the effects of CEP55 overexpression both in vivo and in vitro. In conclusion, CEP55 may enhance the proliferation, invasion, and migration of pNENs by activating the PI3K/AKT/mTOR pathway through its interaction with PI3K. It may serve as a valuable prognostic marker and a promising therapeutic target.

In conclusion, our study provides insights into the molecular landscape governing the LUAD-to-NEC transition, highlighting MUC1 as a potential biomarker. The immune microenvironment is believed to exert a substantial influence on histological transformation, particularly with regards to T cells.

Several differential diagnoses were considered; however, none adequately fit the criteria. The patient remained disease-free for 24 months postoperatively without further adjuvant therapy.

Our study reported poor outcomes with chemotherapy, with a high frequency of retinoblastoma protein (RB) loss and DLL3 positivity. Further clinical developments targeting DLL3 are warranted.

P1, N=2, Terminated, Ascentage Pharma Group Inc. | N=60 --> 2 | Recruiting --> Terminated; Company Strategy

P=N/A, N=14250, Not yet recruiting, Bavarian Cancer Registry | N=9500 --> 14250 | Trial completion date: Aug 2025 --> Aug 2026 | Trial primary completion date: Dec 2024 --> Aug 2025

Integrating PD-1 blockade with tumor-targeted therapy in functioning pitNETs demonstrates synergistic efficacy with enhanced apoptosis, induces cell-cycle arrest, and suppresses hormone secretion using patient-derived primary cell cultures. Altogether, our findings provide an extended resource on the cellular and functional heterogeneity of the pitNET immune microenvironment and offer a conceptual framework for rational therapeutic strategies.

The patient was readmitted to hospital for tumor recurrence and metastasis and received palliative second-line Gemcitabine and cisplatin chemotherapy and three courses of combined immunochemotherapy (Tyvyt [Sintilimab] + Gemcitabine + Cisplatin). For patients with multiple metastases of cholangiocarcinoma, combined immunotherapy could potentially assist in prolonging survival. Currently, there is no standardized treatment for biliary MiNENs, and larger scale studies are needed to establish diagnosis and treatment protocols to improve the overall survival of patients.

Our data show that PAC-1 modulates sunitinib-induced autophagy and blocks lysosomal trapping, potentiating sunitinib activity and increasing death of cancer cells. As both drugs are well-tolerated in patients, the data suggest evaluation of the PAC-1/sunitinib combination in a clinical trial of patients with PNET.

Our observations suggest that LAN suppresses LPS-induced myosin light chain 2 (MLC2), Cofilin, extracellular signal-regulated kinase 1/2 (ERK1/2), STAT1, STAT3, P38 activation; and lung edema. In conclusion, and based on the aforementioned observations, it is suggested that LAN counteracts experimental LPS-induced injury in endothelial cells and mice.

Surgical resection is the treatment of choice for MEN1. The prognosis depends on the site of origin, but early detection and intervention is the most effective.

We then investigate if riboflavin supplementation has the potential to rescue succinate dehydrogenase activity in the intact SDHA catalytic subunit to suppress succinate accumulation even in the absence of SDHB. We show that this latter strategy is not successful.

This consensus statement aims to offer evidence-informed guidance for health care providers involved in the care of patients with MEN1 and associated tumors. It provides guidance on diagnostic tools, genetic testing criteria, imaging techniques, surgical interventions, and posttreatment monitoring. The practical, patient-centered approach outlined in this document is intended to improve outcomes for individuals with MEN1 and other high-risk endocrine tumors.

In addition, we identified potential protein biomarkers for histological subtype classification and risk stratification, which were validated by immunohistochemistry in an independent cohort. This study provides a valuable proteogenomic resource and insight into Lu-NEC heterogeneity.

P=N/A, N=40, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P2, N=32, Not yet recruiting, Washington University School of Medicine

Baseline 177Lu-DOTATATE imaging demonstrated higher lesion uptake and detected more lesions compared to pre-treatment 111In-pentetreotide imaging. Careful interpretation of baseline 177Lu-DOTATATE imaging is essential to avoid misinterpreting the increased number of detected lesions as disease progression. Screening with 111In-pentetreotide imaging may underestimate treatable lesions by PRRT, particularly when planar imaging alone is used, highlighting the need for SSTR PET in pre-treatment evaluation.

Haemato- and nephrotoxicity are the most common toxicities following PRRT. The NETTER‑2 and COMPOSE trials are investigating PRRT with 177Lu-DOTA-TATE/-TOC in G2 and G3 gastroenteropancreatic NETs.

Our results indicate that despite all technical difficulties, multiparametric FC can effectively characterize different types of PitNETs. This enhanced understanding of the immune infiltrate provides valuable insights into PitNET biology and advances clinical diagnostics.

P1/2, N=62, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Oct 2025 --> Dec 2024

LFS is associated with a heightened risk of rapid progression to invasive carcinomas due to TP53 variants. Therefore, earlier initiation of colonoscopy screening may be necessary for patients with LFS.

Although metastatic/multifocal paragangliomas are rare, their occasional relentless course may require complex multidisciplinary treatment in order to maximize neurological as well as oncological outcomes.

Our results revealed that VPA exerts anti-PitNET effects by promoting Drd2 transcriptional activation, thereby inhibiting the mTOR-Pttg1 signaling axis, indicating the potential therapeutic utility of VPA in PitNET treatment.

However, the exact dosimetry for precision oncology, the shortage of radionuclides, and the stability of disease control are still under careful consideration. More high-quality, large-scale prospective studies are essential for obtaining valuable evidence on challenging problems and for further exploration.

This case highlights a rare instance of neuroendocrine tumor metastasis to the breast, assessed using various ultrasound techniques, with detailed imaging and quantitative analysis. The comprehensive multimodal assessment contributes to the limited body of literature and provides elements for the differential diagnosis of a rare breast lesion that should always be considered in the presence of a known primary NET.

These novel miR-mRNA interaction networks identified dysregulated pathways not observed when assessing mRNA alone and provide a foundation for further investigation of their utility as diagnostic and predictive biomarkers.

Next-generation sequencing (NGS) performed on both lesions revealed the presence of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion mutations in both lesions. Notably, the patient achieved a significant therapeutic response to ALK-tyrosine kinase inhibitors (TKIs) targeted therapy..

Qualitative features in contrast-enhanced CT images could be beneficial in differentially diagnosing non-hypervascular PNENs and CA19-9 negative PDACs.

Furthermore, SCLC shows phenotypic plasticity, including neuroendocrine-to-non-neuroendocrine transition driven by NOTCH signalling, which is associated with disease progression, chemoresistance and immune modulation and, in mouse models, with metastasis. Although these features pose substantial challenges, understanding the molecular vulnerabilities of transcription factor subtypes, the functional relevance of plasticity and cell cooperation offer opportunities for personalized therapies informed by liquid and tissue biomarkers.

P2, N=70, Recruiting, National Cancer Institute (NCI) | N=108 --> 70

P=N/A, N=47, Completed, University Hospital, Toulouse | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> May 2024 | Trial primary completion date: Dec 2023 --> May 2024

P2, N=4, Completed, Barbara Ann Karmanos Cancer Institute | Recruiting --> Completed