Table 1.
Potential novel biomarkers in high-grade NET and relative therapeutic agent.
| Molecular Target | Disease | Clinical Correlations | Targeted Therapies | Ref |
|---|---|---|---|---|
| TP53 | NECs | Marker of poor differentiation | None | (10, 16–21, 23–28) |
| KRAS | NECs | Marker of poor differentiation | None | (10, 16–21, 23) |
| RB1 | NECs | Marker of poor differentiation | None | (10, 16–21, 23–29) |
| Lung NETs | Worse prognosis | |||
| MEN1 | GEP NETs | Marker of well differentiation | None | (22, 24–28) |
| Carcinoids | Diagnostic marker | |||
| Worse prognosis (AC) | ||||
| DAXX | GEP NETs | Marker of well differentiation | None | (22) |
| ATRX | GEP NETs | Marker of well differentiation | None | (22) |
| ARID1A | Lung NETs | Pathogenetic role | None | (24, 25) |
| Enhancing mutational burden | ||||
| BRAF | Colorectal NECs | Response to BRAF-MEK inhibition | BRAF-MEK inhibitors | (20–30) |
| DLL3 | GEP NECs | Marker of poor differentiation | Rovalpituzumab tesirine | (27, 31–37) |
| Negative 68Ga-PET | ||||
| Worse prognosis | ||||
| SCLC | Correlated to RB1-loss | |||
| LCNEC | None | |||
| Renal NECs | None | |||
| BRCA | Pancreatic NETs | Response to platinum-based regimes | PARP inhibitors | (22, 38–41) |
| Prostatic NECs | Response to PARP inhibitors | |||
| SLFN11 | SCLC | Response to platinum-based regimes | PARP inhibitors | (42–45) |
| Response to PARP inhibitors | ||||
| ALK | SCLCLCNEC | Worse prognosis | ALK inhibitors | (46–55) |
| NTRK | GEP NECs | Response to NTRK inhibitors | Entrectinib, larotrectinib, taletrectinib | (56–61) |
| SCLC | ||||
| LCNEC | ||||
| PD-L1 | GEP NECs | Marker of poor differentiation | Immune checkpoint inhibitors | (16, 62–70) |
| Worse prognosis | ||||
| Response to immunotherapy | ||||
| SCLC | Response to immunotherapy | |||
| LCNEC | Response to immunotherapy | |||
| H-MSI | Gastric/colorectal NECs | Response to immunotherapy | Immune checkpoint inhibitors | (71–75) |
| TMB | GEP NECs | Response to immunotherapy | Immune checkpoint inhibitors | (21, 76–84) |
| SCLC | ||||
| LCNEC | ||||
| miRNAs | GEP NETs | Diagnostic markers | None | (85–102) |
| Lung NETs | Prognostic markers |
NEC, neuroendocrine carcinoma; GEP, gastroenteropancreatic; NETs, neuroendocrine tumors; SCLC, small cell lung cancer; LCNEC, large cell neuroendocrine carcinoma; AC, atypical carcinoid; KRAS, Kirsten rat sarcoma; RB1, Retinoblastoma 1; MEN1, Menin 1; DAXX, Death Domain Associated Protein; ATRX, alpha-thalassemia/mental retardation, X-linked; ARID1A, AT-Rich Interaction Domain 1A; DLL3, Delta-like protein 3; PARP, Poly[ADP-ribose] polymerase 1; SLFN11, Schlafen 11; ALK, Anaplastic Lymphoma Kinase; NTRK, Neurotrophic receptor tyrosine kinase; PD-L1, programmed cell death protein ligand 1; H-MSI, high microsatellite instability; TMB, tumor mutational burden; miRNA, microRNA.