Cancer drug resistance constitutes a severe limitation for the satisfactory outcome of these patients.This is a complex problem due to the co-existence in cancer cells of multiple and synergistic mechanisms of chemore...Cancer drug resistance constitutes a severe limitation for the satisfactory outcome of these patients.This is a complex problem due to the co-existence in cancer cells of multiple and synergistic mechanisms of chemoresistance(MOC).These mechanisms are accounted for by the expression of a set of genes included in the so-called resistome,whose effectiveness often leads to a lack of response to pharmacological treatment.Additionally,genetic variants affecting these genes further increase the complexity of the question.This review focuses on a set of genes encoding members of the transportome involved in drug uptake,which have been classified into the MOC-1A subgroup of the resistome.These proteins belong to the solute carrier(SLC)superfamily.More precisely,we have considered here several members of families SLC2,SLC7,SLC19,SLC22,SLCO,SLC28,SLC29,SLC31,SLC46,and SLC47 due to the impact of their expression and genetic variants in anticancer drug uptake by tumor cells or,in some cases,general bioavailability.Changes in their expression levels and the appearance of genetic variants can contribute to the Darwinian selection of more resistant clones and,hence,to the development of a more malignant phenotype.Accordingly,to address this issue in future personalized medicine,it is necessary to characterize both changes in resistome genes that can affect their function.It is also essential to consider the time-dependent dimension of these features,as the genetic expression and the appearance of genetic variants can change during tumor progression and in response to treatment.展开更多
基金funding from CIBEREHD,Fondo de Investigaciones Sanitarias,Instituto de Salud Carlos Ⅲ co-funded by European Regional Development Fund/European Social Fund,“Investing in your future”)(PI19/00819,PI20/00189,PI23/00681,and PI22/00526)Junta de Castilla y León(SA074P20,GRS 2322/A/21,and SA113P23)+2 种基金FundacióMarato TV3(Ref.201916-31),Fundación AECC(AECC2023/2027)University of Salamanca(PC_TCUE21-23_011)Spain.Reviejo M was supported by a postdoctoral contract funded by the“Junta de Castilla y Leon”(SA113P23).
文摘Cancer drug resistance constitutes a severe limitation for the satisfactory outcome of these patients.This is a complex problem due to the co-existence in cancer cells of multiple and synergistic mechanisms of chemoresistance(MOC).These mechanisms are accounted for by the expression of a set of genes included in the so-called resistome,whose effectiveness often leads to a lack of response to pharmacological treatment.Additionally,genetic variants affecting these genes further increase the complexity of the question.This review focuses on a set of genes encoding members of the transportome involved in drug uptake,which have been classified into the MOC-1A subgroup of the resistome.These proteins belong to the solute carrier(SLC)superfamily.More precisely,we have considered here several members of families SLC2,SLC7,SLC19,SLC22,SLCO,SLC28,SLC29,SLC31,SLC46,and SLC47 due to the impact of their expression and genetic variants in anticancer drug uptake by tumor cells or,in some cases,general bioavailability.Changes in their expression levels and the appearance of genetic variants can contribute to the Darwinian selection of more resistant clones and,hence,to the development of a more malignant phenotype.Accordingly,to address this issue in future personalized medicine,it is necessary to characterize both changes in resistome genes that can affect their function.It is also essential to consider the time-dependent dimension of these features,as the genetic expression and the appearance of genetic variants can change during tumor progression and in response to treatment.
