Table 2 Current molecular pathway based therapies in head and neck cancer

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: 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]

in vitro and mouse model: Radiosensitization of SCC-1, SCC-9, A431, and KB HNSCC cell lines with curcumin

[189, 190]