Neuroendocrine Tumor

Mitochondrial biogenesis facilitated cisplatin resistance and inhibition of UPRmt resensitizes CRPC-NE cells to cisplatin. Together, our findings demonstrated that UPRmt promotes mitochondrial health via upregulating β-catenin signaling and UPRmt represents viable therapeutic target for NEPC.

68Ga-pentixafor uptake was associated with CXCR4 expression and ACTH level.

Nottingham grade, rather than GEP grade, holds important prognostic significance in primary breast NETs. Nottingham G3 NETs represent a small proportion of breast NETs, and may demonstrate distinct clinicopathological and molecular features from other high-grade breast carcinomas with diffuse neuroendocrine markers expression.

In each case, checkpoint blockade led to durable radiographic responses. We therefore propose that it is reasonable to assess combined positive score and tumor mutational burden in refractory or recurrent pancreatic cancers when initiation of ICB is being considered.

This case highlights the importance of recognizing dedifferentiation in CSF SFTs, which often correlates with aggressive tumor behavior and poor prognosis. Given the rarity of neuroendocrine "transdedifferentiation," this case adds valuable insight into the diverse dedifferentiation patterns seen in CNS SFTs, emphasizing the need for accurate diagnosis to guide appropriate treatment strategies.

On occasion, the intensity of physiologic uptake in these structures can be pronounced enough to mimic metastatic disease, posing a diagnostic challenge. Awareness of this rare phenomenon is essential to avoid misdiagnosis and unnecessary interventions.

The recent identification of several other key novel drivers of NE transdifferentiation, including MYCN, ASCL1, BRN2, ONECUT2, and FOXA2, further elucidates the complex regulatory networks and pathways involved in this process. We suggest that, given the multifactorial nature of NEPC, novel therapeutic strategies that combine multiple modalities are essential to overcome therapeutic resistance and improve patient outcomes.

PET/CT with [68Ga]-DOTA-peptides can detect parathyroid NENs. The incidental detection of high [68Ga]-DOTA-peptide uptake in the parathyroid region during whole-body PET/CT may prompt biochemical evaluation for PHPT. We suggest that endothelial SST expression mediates high radiopharmaceutical uptake by PAs and that SSA treatment can reduce hypercalcemia in PHPT patients.

In ONB, relative to SNUC and SNEC, the SSTR2 expression profile, combined with its immune profiles, indicates potential novel therapeutic strategies and combinations for this unmet clinical need. Conversely, the inflammatory microenvironment of SNUC may be targetable using immuno-oncologic therapies.

Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.

On microscopic evaluation, the tumor was composed of solid nests and sheets of small rounded cells, and on Immunohistochemical (IHC) evaluation, the tumor cells showed intense cell-membranous immunoactivity for MIC2 protein (CD99). In the differential diagnosis of any invasive pelvic tumor in young women, pPNET should be considered.

Lastly, NKX2-1/FOXA2 interacts with, and recruits CBP/p300 proteins to activate NE enhancers, and pharmacological inhibitors of CBP/p300 effectively blunted NE gene expression and abolished NEPC tumor growth. Thus, our study reports a hierarchical network of TFs governed by NKX2-1 in regulating the 2D and 3D chromatin re-organization during NET and uncovers a promising therapeutic approach to eradicate NEPC.

NPC is a rare malignancy with significant geographical variations in incidence rates. Somatostatin receptor 2 (SSTR2) expression in NPC is well documented and can serve as a potential theragnostic marker in advanced NPC where the successful outcome is minimal with currently available treatment modalities.

On planar scintigraphy, the gallbladder uptake could have been misidentified as liver metastasis. By utilizing single photon emission computed tomography/computed tomography imaging, we were able to precisely localize the tracer and obtain anatomical morphological characteristics, thereby averting the potential for misinterpretation of liver metastasis resulting from the gallbladder's physiological uptake of [ 177 Lu]Lu-DOTATATE in NET patients.

Multidisciplinary consultation recommended initiation of systemic chemotherapy with cisplatin and etoposide. This case underscores the aggressive nature and poor prognosis associated with malignant insulinomas, particularly those with high proliferative indices. It highlights the complexities of managing refractory hypoglycemia in the context of widespread metastatic disease and emphasizes the urgent need for effective therapeutic strategies to improve patient outcomes.

Improved imaging modalities and modifications in specific therapies as components of multimodal treatment concepts are concordant with significantly improved survival outcomes in NELM over 30 years. The use of multimodal therapy improved overall survival in patients with NE LM. Future studies should determine optimal treatment selection and sequencing, and role of novel biomarkers to guide these.

P1/2, N=105, Recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Not yet recruiting --> Recruiting | Initiation date: Jun 2024 --> Sep 2024

P1, N=65, Recruiting, Abdera Therapeutics Inc.

P1/2, N=78, Recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Not yet recruiting --> Recruiting

P=N/A, N=60, Not yet recruiting, Nantes University Hospital

RET pathogenic variant (p.Cys634Trp) associated with MEN2A syndrome was the most prevalent in Romanian population with PPGLs and could be considered as a founder effect. Patients with hereditary disease are diagnosed at a younger age and develop bilateral tumors more frequently compared to sporadic cases.

For diagnostic purposes, taking into account, Rb status improved, but only marginally, the performances of p53 status. In conclusion, our study underlines the molecular heterogeneity of NET-G3 and LCNEC, irrespectively of the primary, and provides further insight on the diagnostic relevance of p53/Rb immunodetection in high-grade neuroendocrine neoplasms.

P1, N=24, Not yet recruiting, Peking University Cancer Hospital & Institute

P2, N=322, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2027 --> Jun 2029 | Trial primary completion date: Feb 2027 --> Jun 2029

P3, N=332, Active, not recruiting, Camurus AB | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2025

Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs), such as alectinib and crizotinib, have been used in the treatment of NET patients with ALK rearrangement. The patient received ensartinib (225 mg/day) for 18 months until disease progression in June 2024 and achieved a radiographic partial response. Although patients with ALK fusions showed response to ensatinib in nonsmall cell lung cancer (NSCLC), this study first reports a metastatic NET case with a novel CEP44-ALK rearrangement that responded favorably to ensartinib.

Sunitinib for c-KIT mutations did not meet the primary end point, but in this small sample size, a potential signal cannot be ruled out. Rate of eligible c-KIT mutations was low, affecting accrual to this arm.

No abstract available

in our series BNENs mainly affect a post-menopausal population and luminal A pattern is the most frequent immunophenotype. As expected, lymphatic infiltration is most frequently reported in invasive breast cancer with neuroendocrine differentiation; necrosis is absent in well-differentiated neuroendocrine carcinomas. Synaptophysin and chromogranin A are important markers for the diagnosis of BNEN.

P=N/A, N=100, Recruiting, Azienda Ospedaliera Universitaria Integrata Verona | Not yet recruiting --> Recruiting

In conclusion, our data demonstrate significant levels of CLDN3 expression in many different tumor entities and identify reduced CLDN3 expression as a potential prognostic marker in RCC.

The present report describes a specific case of PNENB, which was consistent with the morphological and molecular features of other cases in most previous studies. In addition, the current body of literature on PNENB, including its development, diagnosis, molecular features, treatment and prognosis is reviewed.

P2, N=67, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial primary completion date: Jan 2025 --> Jun 2025

These findings highlight the importance of integrating advanced imaging techniques and recognizing the need for more nuanced criteria in assessing the efficacy of PRRT in NET patients. This approach aims to enhance the accuracy of treatment monitoring and improve patient outcomes.

23ME-00610 has mild-to-moderate on-target adverse events and PK/PD consistent with tumor target saturation and dosing Q3W. The trend for clinical benefit in participants with tumor CD200 expression suggests 23ME-00610 inhibits CD200R1 signaling and may reverse CD200-mediated immune evasion. Based on PK/PD, safety, and preliminary anti-tumor activity, 1400 mg Q3W was selected as the dose for further study.

We have also collated studies pertinent to MENIN function in the literature and summarised the impact of MEN1 variants on 74 biological variables. We propose a set of four MEN1 variants, MENINL22R, MENINH139D, MENINA242V and MENINW436R, that represent a cohort with different biological properties, which should be investigated concurrently to better dissect MENIN function.

The longest ECS remission and CMR continues at >17 years. PRRT can be effective for ECS caused by metastatic SSTR-positive GEPNEN and should be considered in its treatment algorithm.

P2, N=120, Recruiting, Melanoma and Skin Cancer Trials Limited | Trial completion date: Apr 2028 --> Apr 2030

Clinically, ISO behaved similarly to HYPER. Further studies are needed to unify SI assessment and improve its clinical applicability in acromegaly.

P1, N=24, Recruiting, University Hospital, Basel, Switzerland | Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Jun 2024 --> Jun 2026

PNETs in Korean patients with MEN1 exhibit a stable prognosis. An individualized follow-up strategy may be necessary, particularly for young patients with truncating mutation in the MEN1 gene. In addition, those with mutations in exons 3 or 10 may require more active surveillance to decrease the risk of progression.

P2, N=4, Completed, National Cancer Institute (NCI) | Recruiting --> Completed | N=25 --> 4 | Trial completion date: Dec 2026 --> Feb 2024