Table 2.
Potential molecular targets and corresponding medical treatments for CPs.
| Molecular or Genetic Alterations | CPs Type (% of Case) |
Tumoral Compartment or Specific Tumoral Cell | Molecular or Biological Disarrangement | Possible Molecular Treatment |
|---|---|---|---|---|
| BRAFV600E | PCP (95–100%) |
SOX2+/Height proliferating progenitor tumor cell | Hyperactivation MAPKK pathway | BRAF/MEKi [16] |
| CTNNB1 (Exon 3 Beta catenin gene) |
ACP (70–100%) |
Single or cell clusters (SOX2+) in tumor mass or at the base of epithelial protrusion |
Hyperactivation WNT/beta catenin pathway leading to SASP | Senolytics [53] Wnt/β-catenin signaling inhibitors (several on-going trials) [54] |
| CTNNB1 (Exon 3 Beta catenin gene) |
ACP (70–100%) |
Forefront or leading edge of the tumor | Hyperactivation MAPK pathway (possible crosstalk with WNT pathway) | Trametinib or combined BRAF/MEKi [29] |
| CTNNB1 (Exon 3 Beta catenin gene) |
ACP (70–100%) |
Single or cell clusters (SOX2+) in tumor mass or at the base of epithelial protrusion (ACP recurrence) |
SHH secretion and hyperactivation of SHH pathway IL-1 and IL-6 secretion Secretion of VEGF, FGF2, TGF beta and increased expression of PDGFR-alpha Hyperactivation of EGF/EGFR pathway (AREG, EGFR, and ERBB-3) |
SHH pathway inhibitors (vismodegib) [1] IL-1R inhibitor (anakinra) Antiangiogenic drugs [55]: * bevacizumab * Selctive-PDGFR-alfa blockers (ripretinib) TKI: cetuximab, erlotinib, and lapatinib [15] |
| CTNNB1 (exon 3 Beta catenin gene) |
ACP (70–100%) |
Single or cell clusters (SOX2+) in tumor mass or at the base of epithelial protrusion |
MMP9 and MMP12 overexpression [56] LCK, EPHA2, SRC overexpression [56] |
MMP9/12 inhibitor AZD1236 dasatinib |
| PD1/PDL-1 | ACP (100%) PCP (100%) |
Cyst-lining in ACP, and to basal tumor cells in PCP | Immunomodulatory action | ICI [49] |
| PIK3CA and the TSC2 mutations [57] | ACP (-) PCP (-) |
_ | Hyperactivation of mTor pathway | Everolimus (mTor inhibitors) Copanlisib (pan-PIK3 inhibitor) |
LCK: lymphocyte-specific protein tyrosine kinase; EPHA2: ephrin type-A2; SRC: proto-oncogene tyrosine-protein kinase Src; SHH: sonic hedgehog; TKI: tyrosine kinase inhibitors; ICI: immune checkpoint inhibitors; BRAF/MEKi: BRAF (ex. dabrafenib) and MEK (ex. trametinib) inhibitor agents; SASP: pro-tumorigenic senescence-associated secretory phenotype; mTor: mammalian target of rapamycin; PIK3CA: phosphatidylinositol 3-kinase; TSC2: tuberous sclerosis complex 2.