用于头颈肿瘤鳞癌靶向治疗的分子靶标和相应抑制剂

Table 1 Molecular targets and their inhibitors used for HNSCC therapy.

分子靶标/抑制剂	种类	作用机制	剂量限制性毒性作用
一、Erb family (EGFR, HER2, HER3, and HER4)
西妥昔单抗/Cetuximab	Recombinant human/mouse chimeric IgG1 monoclonal antibody	Binds EGFR and inhibits activation of receptor tyrosine kinase (RTK) Stimulates receptor internalization and down-regulation from the cell surface	Acne-like rashes, fever and chills, asthaenia, transaminase level increase, nausea
帕妥珠单抗/Pertuzumab	Humanized mAb for HER2	Inhibits ligand-activated HER dimerization with HER2, thus inhibiting activation of intracellular signalling	Acne-like rashes
帕尼突单抗/Panitumumab	Humanized EGFR mAb (IgG2)	Binds to extracellular domains of EGFR	Acne formation
Martuzumab	Humanized EGFR mAb (IgG1)	Binds to extracellular domains of EGFR	Headache and fever
曲妥珠单抗/Trastuzumab	HER2/neu antibody	Complement- and antibody-dependent cell-mediated cytotoxicity	Cardiac dysfunction, renal failure, membranous nephropathy and glomerulonephritis
二、 Tyrosine kinase
吉非替尼/gefitinib	Synthetic small molecule	Targets EGFR tyrosine kinase domain	Skin rash, diarrhoea, nausea and emesis
厄洛替尼/erlotinib	Synthetic small molecule	Inhibitor of EGFR	Skin rashes, dry skin and diarrhoea
拉帕替尼/lapatinib	Synthetic small molecule	Inhibits EGFR and HER2/neu heterodimer	Diarrhoea, nausea, fatigue and anorexia
三、VEGF
贝伐珠单抗/Bevacizumab	Humanized recombinant mAb	Antibody directed against VEGF	Hypertension, proteinuria, bleeding and thrombosis
四、Multikinase inhibitor
索拉非尼/Sorafenib	Synthetic molecule	Serine/threonine Raf-1 kinase; receptor tyrosine kinases, including EGFR, PDGFR, KIT and Flt3	Hypothyroidism
Nintedanib/BIBF 1120	Synthetic molecule	Inhibitor of VEGF, PDGF and FGF	Nausea, vomiting, diarrhoea, abdominal pain, fatigue and asymptomatic, reversible liver enzyme elevations
舒尼替尼/Sunitinib	Synthetic molecule	Inhibits PDGFR, EGFR, stem cell factor receptor (KIT) and Flt, HER2/neu
凡德他尼/Vandetanib (ZD6474)	Synthetic molecule	Inhibitor of VEGFR, EGFR, and rearranged during transfection (RET) tyrosine kinases
五、PI3K/Akt/mTOR
Temsirolimus	Synthetic molecule	mTOR
六、HSP90 inhibitor
Geldanamycin	Benzoquinone ansamycin antibiotic	Degrades HSP90
七、Proteasome inhibitor
Bortezomib	Synthetic molecule	Proteasome inhibitor	Peripheral neuropathy, neutropenia and thrombocytopenia

资料来源：K. Alok Pathak, Richard W. Nason. Potential Molecular Targets: From Bench to Bedside in Controversies in Oral Cancer. Springer, 2012.