表皮生长因子受体酪氨酸激酶抑制剂对骨组织的影响研究进展

Advances in the effects of epidermal growth factor receptor tyrosine kinase inhibitors on bone tissue

表皮生长因子受体(EGFR)是原癌基因c-erbB-1的表达产物,具有酪氨酸激酶活性。EGFR与配体结合可以激活下游信号通路并导致肿瘤细胞的增殖及侵袭。在肿瘤细胞中,EGFR过度表达可以激活骨吸收过程,导致肿瘤骨转移。表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)主要包括吉非替尼、厄洛替尼、阿法替尼、奥希替尼等,这些药物可以抑制骨吸收和肿瘤骨转移,但也会导致骨形成障碍。联合用药可以解决耐药等问题,并改善药物对骨组织的影响。本文对常见的EGFR-TKIs在骨形成、骨吸收和肿瘤骨转移等过程中对骨组织的影响及其机制进行综述,对不同EGFR-TKIs联合用药的优点及其对骨组织的影响进行归纳,并就EGFR-TKIs对骨组织负面影响的解决方案进行展望。

Epidermal growth factor receptor(EGFR)is an expression product of the proto-oncogene c-erbB-1 with tyro-sine kinase activity.EGFR binds to ligands to activate downstream signaling pathways and leads to tumor cell proliferation and invasion.In cancer cells,overexpressed EGFR can activate the bone resorption process,resulting in bone metastasis of the tumor.EGFR-tyrosine kinase inhibitors(EGFR-TKI)mainly include gefitinib,erlotinib,afatinib,osimertinib and so on.These drugs can relieve the bone resorption process and tumor bone metastasis,but they also can cause bone formation disorders.Combination medications can address issues such as drug resistance,and improve the effects of the drugs on bone tissue.In this paper,the effects and mechanisms of common EGFR-TKIs on bone tissues in the processes such as bone formation,bone resorption and tumor bone metastasis were reviewed,and the advantages of different EGFR-TKIs combinations and their effects on bone tissues were also summarized.The solutions to the negative effects of EGFR-TKIs on bone tissue were also prospected.