Advances in medical treatment for pancreatic neuroendocrine neoplasms

Figure 1 History and key events in the development of pancreatic neuroendocrine neoplasms systemic therapy. PRRT: Peptide receptor radionuclide therapy; SSAs: Somatostatin analogs; PD-L1: Programmed cell death-ligand 1 inhibitor; PD-1: Programmed cell death-1 inhibitor; CTLA-4: Cytotoxic T-lymphocyte antigen 4 inhibitor; STZ: Streptozotocin; CAPTEM: Capecitabine and temozolomide regimen; PROMID[13], NCT00171873; CLARINET[14], NCT00353496; SUN.III[15], NCT00428597; RADIANT-3[16], NCT00510068; SANET-P[17], NCT02589821; NETTER-1[18], NCT01578239.

Figure 2 Molecular mechanisms of the action of somatostatin analog, antiangiogenic agents, everolimus, temozolomide, olaparib, and metformin on pancreatic neuroendocrine neoplasms and interactions. FGFR: Fibroblast growth factor receptor; EGFR: Epidermal growth factor receptor; VEGFR: Vascular endothelial growth factor receptor; IGF-1: Type 1 insulin-like growth factor; IGF-1R: Type 1 insulin-like growth factor receptor; SSTR: Somatostatin receptor; PI3K: Phosphoinositide 3-kinase; PIP2: Phosphatidylinositol-4,5-bisphosphate; PIP3: Phosphatidylinositol-3,4,5-triphosphate; AKT: Protein kinase B; mTORC1: Mechanistic target of rapamycin complex 1; mTORC2: Mechanistic target of rapamycin complex 2; IRS1: Insulin receptor substrate 1; AMPK: Adenosine 5’-monophosphate-activated protein kinase; TSC1: Tuberous sclerosis complex 1; TSC2: Tuberous sclerosis complex 2; SOS: Son of sevenless; RAS: Rat sarcoma virus; RAF: Rapidly accelerated fibrosarcoma; MEK: Methyl ethyl ketone; ERK: Extracellular signal-regulated kinase; BER: Base-excision repair; MGMT: O6-methylguanine DNA methyltransferase; PARP: Poly (ADP-ribose) polymerase. Citation: Created with BioRender.com.