Tyrosine kinase inhibitors(TKIs)are the key agent in the treatment of renal cell carcino-ma(RCC)so far.Drugs such as sunitinib and sorafenib showed significant benefits RCC patients,however,the adverse effect,drug efficacy and drug resistance limited the use of these therapy.Espe-cially the drug resistant issue brings up a big chal-lenge for clinical practice,and the mechanisms un-derlying are still poorly understood.In recent years,new therapies have been combined with TKIs to improve the treatment outcome.Immuno-therapy,combination therapy with other TKIs,tar-geted nanoparticle delivery,and drug modification are widely studied to improve the efficacies of TKIs and regain the sensitivity.In this review,we sum-marizes the current understanding of TKI drug resis-tance and the approaches to regaining drug sensi-tivity.

Tyrosine kinase inhibitors(TKIs)are the key agent in the treatment of renal cell carcino-ma(RCC)so far.Drugs such as sunitinib and sorafenib showed significant benefits RCC patients,however,the adverse effect,drug efficacy and drug resistance limited the use of these therapy.Espe-cially the drug resistant issue brings up a big chal-lenge for clinical practice,and the mechanisms un-derlying are still poorly understood.In recent years,new therapies have been combined with TKIs to improve the treatment outcome.Immuno-therapy,combination therapy with other TKIs,tar-geted nanoparticle delivery,and drug modification are widely studied to improve the efficacies of TKIs and regain the sensitivity.In this review,we sum-marizes the current understanding of TKI drug resis-tance and the approaches to regaining drug sensi-tivity.