Table 1.
Partial list of emerging targets; their functions in cellular processes (malignancy characteristics), mechanism(s) of action, and signaling flow-through; and potential drugs or strategies to improve HR-NB treatment.
| Target | Function/Strategy | Targets/Signaling | Therapeutic strategy | Ref. |
|---|---|---|---|---|
| MDA-9/SYNTENIN | ↑Metastasis, ↑EMT, ↓OS | ↑Src, ↑FAK, ↑NFkB, ↑Slug, ↑MMP2, ↑MMP9. ↑integrin→SRC→RHO→RAC→CDC42 | PDZ1i, MDA-siRNA, peptide | [121,122] |
| GLS2 | ↓Proliferation, ↑Cell cycle arrest | ↓cMYC | [123] | |
| P27kip1 | ↓Progression | MYC→CKS1→SKP2→P27kip1 | Prozac | [124] |
| KLF9 | ↑Differentiation, ↓Proliferation, ↓Invasion | ↓SHH binding to the promoter, ↓GUI, | [125] | |
| WRD5 | ↑Proliferation, ↑Tumorosphere formation | ↑MYC, CARM↑, ↑H3K4me3 | [126] | |
| MZF1 | ↑Glycolysis | ↑HK2, ↑PGKI, ↑YY1 | 21-AA-MZF1-uPEP | [127] |
| SNAI2 | ↑Self-renewal, ↑EMT, ↑RA-resistance, ↓Differentiation | ↓NRCAM, ↓CDH5 | CRISPR-Cas9, shRNA | [128] |
| Stmn | ↑Migration, ↑Invasion | ↑PTPN14, miRs ↑(3935, 1281, 4682, 222, 221, 620, 488) ↓(382, 935, 4656, 132, 4492) | PTPN14-shRNA | [129] |
| ITCH | ↓Apoptosis, ↑Radioreistance | ↓TP73 | siRNA-NPs | [130] |
| PLPR1 | ↓Cell-migration, ↑Adhesion | ↓RAC1 | [131] | |
| TRKB | ↑Entrectinib resistance | ↑ERK/MAPK, ↓PTEN | [132] | |
| BARD1 | ↑DNA damage after RT, ↑Apoptosis, ↑G2/M cell cycle | ↑IGFIR, ↑P75 | BARD1-FL | [133] |
| YAP1 | ↑Trametinib resistance, ↑Cell viability, ↑Proliferation | ↑MAPK, ↑E2F, ↑MYCN, ↑P27KIP1-NL, ↑AKT | Lv-CRISPR-YAP1-null-NLF | [134,135] |
| TERT | ↓Prognosis, ↑Oncogenic pathway | ↑BRD4, H3K27AC, H3K36me3 | BRD4i (AZD5153), CDKi (dinacictib) | [136] |
| PNUTS | ↑Proliferation | ↑MYCN Protein | CDKTi (THZ1) + TKI | [137] |
| MYCN-LM01-ASCL1 | ↓Differentiation | ↓NTRK/TRKA, ↓NPY | Ponatinib, Lapatinib | [138] |
| GX15–070→↓ BCl2 | ↑Prosurvival autophagy, ↓Apoptosis | ↑LC3II | GX15–070 + HCQ | [139] |
| Hypomethylation of GATA3 | ↑Proliferation, ↑G2-M, ↓PARP cleavage | ↑GATA3 Protein, ↑CCND1 | GATA3-siRNA | [140] |
| PIM1 | ↑ALKi resistance, ↓Apoptosis | PIM1i (AZD1208) + Ceritinib | [141] | |
| GOLPH3 | ↑DNA repair, ↑Therapy resistance | ↑TPX2, ↑MY018A | [142] | |
| AURKA, AURKB | ↓Apoptosis, ↓G2-M | ↑PGAM2, ↑ACADM | AURKi - Tozasertib (VX-680) | [143] |
| PTPN1P | ↑Proliferation | PTPN1-siRNA | [144] | |
| RAD51 | ↑Chemoresistance | Lv-shRNA | [145] | |
| MCPIP1 | ↓Proliferation, ↑G1 phase | ↓Cyclins A1, b1, D1, D3, E1, E2, ↓CDK2P, ↓CDK4 P, ↓RB | [146] |