Phenotypic and functional characteristics of pituitary adenoma stem cells

Table 2 Pituitary adenoma stem cells: Markers, pathways, models, phenotypes, and translational targets

Domain	Key elements	Representative examples/notes	Translational implications
Markers of stemness	Transcription factors; surface markers	SOX2, OCT4, NANOG; CD133, Nestin	Facilitate the identification of PASC and the prospective categorization of patients based on biomarkers
Experimental models	In vitro; in vivo; ex vivo	Sphere-forming assays, organoids, xenografts	Simulate tumor-propagating cell dynamics and evaluate pathway inhibitors
Signaling pathways	Core developmental cascades	Wnt/beta-catenin, Notch, SHH-GLI, PI3K/AKT/mTOR, JAK/STAT	Facilitate self-renewal, plasticity, invasion, and therapeutic resistance
Associated phenotypes	Cellular functions	Self-renewal, multipotency, epithelial–mesenchymal transition (EMT), drug resistance	Phenotypic characteristics of aggressive PitNETs
Therapeutic targets	Current and emerging strategies	Somatostatin receptor ligands (SRLs), dopamine agonists, temozolomide, PRRT; experimental Notch or Wnt inhibitors	Integrate endocrine regulation with therapies aimed at stemness
Clinical context	Disease entities and therapies	Acromegaly: Oral SST2 agonist paltusotine, oral octreotide capsules; Cushing’s: Osilodrostat, relacorilant; Aggressive PitNETs: TMZ, PRRT, ICIs	Exhibit the expanding translational pipeline and justification for combinatorial approaches

SOX2: SRY-related HMG-box transcription factor 2; OCT4: Octamer-binding transcription factor 4; SHH-GLI: Sonic hedgehog signaling molecule/glioma-associated oncogene homolog 1 (Zinc finger protein); PI3K/AKT/mTOR: Phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin; EMT: Epithelial–mesenchymal transition; SRLs: Somatostatin receptor ligands; SST2: Somatostatin receptor 2; JAK/STAT: Janus kinase/signal transducer and activator of transcription; PASC: Pituitary adenoma stem cells; PitNET: Pituitary neuroendocrine tumor; SRL: Somatostatin receptor ligand; TMZ: Temozolomide; PRRT: Peptide receptor radionuclide therapy; ICI: Immune checkpoint inhibitor.