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/CetuximabRecombinant human/mouse chimeric IgG1 monoclonal antibodyBinds EGFR and inhibits activation of receptor tyrosine kinase (RTK) Stimulates receptor internalization and down-regulation from the cell surfaceAcne-like rashes, fever and chills, asthaenia, transaminase level increase, nausea
帕妥珠单抗/PertuzumabHumanized mAb for HER2Inhibits ligand-activated HER dimerization with HER2, thus inhibiting activation of intracellular signallingAcne-like rashes
帕尼突单抗/PanitumumabHumanized EGFR mAb (IgG2)Binds to extracellular domains of EGFRAcne formation
MartuzumabHumanized EGFR mAb (IgG1)Binds to extracellular domains of EGFRHeadache and fever
曲妥珠单抗/TrastuzumabHER2/neu antibodyComplement- and antibody-dependent cell-mediated cytotoxicityCardiac dysfunction, renal failure, membranous nephropathy and glomerulonephritis
二、 Tyrosine kinase
吉非替尼/gefitinibSynthetic small moleculeTargets EGFR tyrosine kinase domainSkin rash, diarrhoea, nausea and emesis
厄洛替尼/erlotinibSynthetic small moleculeInhibitor of EGFRSkin rashes, dry skin and diarrhoea
拉帕替尼/lapatinibSynthetic small moleculeInhibits EGFR and HER2/neu heterodimerDiarrhoea, nausea, fatigue and anorexia
三、VEGF
贝伐珠单抗/BevacizumabHumanized recombinant mAbAntibody directed against VEGFHypertension, proteinuria, bleeding and thrombosis
四、Multikinase inhibitor
索拉非尼/SorafenibSynthetic moleculeSerine/threonine Raf-1 kinase; receptor tyrosine kinases, including EGFR, PDGFR, KIT and Flt3Hypothyroidism
Nintedanib/BIBF 1120Synthetic moleculeInhibitor of VEGF, PDGF and FGFNausea, vomiting, diarrhoea, abdominal pain, fatigue and asymptomatic, reversible liver enzyme elevations
舒尼替尼/SunitinibSynthetic moleculeInhibits PDGFR, EGFR, stem cell factor receptor (KIT) and Flt, HER2/neu
凡德他尼/Vandetanib (ZD6474)Synthetic moleculeInhibitor of VEGFR, EGFR, and rearranged during transfection (RET) tyrosine kinases
五、PI3K/Akt/mTOR
TemsirolimusSynthetic moleculemTOR
六、HSP90 inhibitor
GeldanamycinBenzoquinone ansamycin antibioticDegrades HSP90
七、Proteasome inhibitor
BortezomibSynthetic moleculeProteasome inhibitorPeripheral neuropathy, neutropenia and thrombocytopenia
Fig. 1 Signaling pathways frequently deregulated in HNSCC

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

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