Table 2.
Current molecular pathway based therapies in head and neck cancer
| Agent | Molecular target | Phase/model of investigation in HNSCC | Reference |
|---|---|---|---|
| Erlotinib/Gefitinib/Lapatinib | Anti-EGFR receptor kinase | Erlotinib: Phase II study in refractory/metastatic HNSCC Gefatinib: PhaseIII vs methotraxate in recurrent HNSCC |
[205-207] |
| Bevacizumab | Anti-VEGF monoclonal antibody | Mouse xenograft models: in combination with paclitaxel Phase I/II trial of bevacizumab and erlotinib in recurrent/metastatic HNSCC |
[208] |
| Rapamycin derivatives (Everolimus, Deferolimus Temserolimus) |
Inhibition of PI3K/AKT/mTOR pathway | Mouse xenograft model: Single agent CCI-779 in minimal residual disease Mouse xenograft model: CCI-779 in combination with radiotherapy |
[210-212] |
| Sorafenib | Multikinase inhibitor targeting MAP kinase, VEGFR, PDGFR FLT3, Ret, c-kit | Phase II: in chemotherapy-naïve persistent/recurrent HNSCC | [213,214] |
| Pemetrexed | Folate antimetabolite | Phase I: in combination with cisplatin in HNSCC Phase II: Pemetrexed plus gemcitabine in recurrent/metastatic HNSCC |
[215,216] |
| Bortezomib | Proteosome inhibitor | Phase I: Bortezomib with re-irradiation in HNSCC Phase II: Bortezomib with docetaxel in recurrent/metastatic HNSCC in vitro: Synergistic anti-tumor effect of Bortezomib and cisplatin in HNSCC cell lines |
[217-219] |
| Curcumin | Inhibition of NF-kB activation, Suppression of interleukins, Cell cycle inhibition, Suppression of VEGF and other angionegic factors, Up-regulation of cellular adhesion molecules, inhibition of STAT 3 | in vitro: Growth suppression of HNSCC cell lines with decreased NF-kB activation | [48,53] |
| in vitro: Suppression of IL-6 and IL-8 expression in HNSCC | [180] | ||
| in vitro: Growth suppression of immortalized epithelial cells | [178,187] | ||
| Mouse xenograft: Suppression of CAL 27 cell line tumors | [48,53] | ||
| Mouse model: Inhibition of oral carcinogenesis | [178,187] | ||
| in vitro and mouse model: Synergistic anti-tumor effect of Curcumin and cisplatin in CAL 27 and UM-SCC1 cell lines | [188] | ||
| in vitro and mouse model: Radiosensitization of SCC-1, SCC-9, A431, and KB HNSCC cell lines with curcumin | [189,190] |