MEN1 (Menin 1)

These findings indicate that SCG2 is a potential prognostic marker and therapeutic target for pNETs. It may be involved in disease progression by modulating the tumor immune microenvironment, suggesting a possible role in prognostic evaluation and clinical management.

Furthermore, clinical data revealed that NF-PanNET patients with prior metformin use exhibited improved prognosis. These findings demonstrate that blood glucose control through metformin represents a promising preventive and therapeutic strategy for NF-PanNETs and MEN1-associated neuroendocrine tumors.

He was referred for parathyroidectomy followed by total pancreatectomy with duodenectomy, while first-degree relatives were offered genetic screening. This case highlights the diagnostic complexity of MEN1 in the absence of a family history, in which gastrointestinal ulcerations with bleeding, fleeting thrombophlebitis, and hypercalcemia may serve as early clinical clues.

In an overwhelming majority of patients with MEN1, radiological surveillance for non-functional pituitary adenomas offers minimal added benefit beyond patient-reported symptoms and pituitary function testing.

The mutations were statistically associated with age, higher serum calcium levels, elevated ALP, and greater skeletal involvement. For optimal management, PHPT patients with high-risk features should be subjected to customised genetic testing in resource-limited settings.

Approximately 5-10% of NETs are associated with hereditary syndromes, though recent findings suggest germline pathogenic variants, which were present in additional 5% of apparently sporadic NETs and NECs, requiring further study. An integrated histological, molecular, and clinical approach is essential to improve the classification, prognostication, and management of NENs, while recognizing the distinct biology of individual subtypes.

Menin inhibitor approval/use is expanding into other HOX-driven subtypes (e.g. NPM1, NUP98r), as frontline option and in combination settings. Monitoring for differentiation syndrome, QT interval prolongation, recognizing pseudo-progression, and supportive care needs remains essential to maximize patient benefit.

This case study looks at a family with four affected members over two generations who have been diagnosed with the syndrome after next generation sequencing identified a novel Alu insertion. Previous genetic testing in the index patient had not identified an underlying cause.

While taxanes such as docetaxel (Dtx) and cabazitaxel (Cbz) are widely employed, therapeutic resistance remains a major clinical obstacle...Moreover, combination treatment with the mTOR inhibitor Torin-1 and docetaxel synergistically enhanced therapeutic response in Menin-depleted resistant cells. MEN1 knockdown also abrogated tumor growth in vivo.These findings identify Menin as one of the key mediator of taxane resistance in CRPC through the regulation of mTOR. Targeting Menin, alone or in combination with mTOR inhibition, represents a promising strategy to overcome resistance and improve therapeutic outcomes in taxane-refractory PC.

TYMS levels also impact the efficacy of everolimus, an FDA-approved mTOR inhibitor for patients with PanNET, underscoring the clinical significance of our findings. In summary, our study uncovers a new role of TYMS linking nucleotide metabolism to growth signaling pathways via the regulation of the AMPK-mTOR axis.

CAFs can promote GC progression by delivering Menin-containing exosomes, which activates the HSPA6/JNK/JunD pathway and induces EMT. Targeting Menin within CAFs and GC cells and blocking the delivery of Menin by exosomes may provide novel strategies for GC treatment.

The 84 patients (63% KMT2Ar, n=53; 23% NPM1c, n=19) who received MENINi were heavily pre-treated: 86% (n=72) had prior intensive chemotherapy (IC), 77% venetoclax (VEN, n=67), and 38% (n=32) allogeneic stem cell transplantation...Of the 60% (n=50) that were treated, common regimens were hypomethylating agent (HMA)/VEN (26%, n=13), clinical trial (26%, n=13), and gilteritinib-based therapy (18%, n=9)...All CR/CRi occurred with HMA/VEN (n=2, 15%), IC+VEN (n=4, 67%), or MENINi switching (bleximenib to revumenib, n=1, 50%)...Outcomes after MENINi failure are poor, but responses occur with VEN-based regimens or MENINi switching. FLT3-ITD, WT1, and MEN1 mutations are associated with resistance.