Focus

UNDERSTANDING THE BASIS OF CANCER RESISTANCE TO THERAPEUTIC DRUGS

Resistance to cancer chemotherapeutics, e.g. taxanes and anthracyclines, is largely due to the overexpression of efflux pumps, in particular ABCB1 (P-glycoprotein or MDR1). Resistance leads to poor clinical outcome. Overexpression of a group of genes that surround the ABCB1 genomic locus (the ABCB1 amplicon), including Sorcin (SRI), may contribute to the establishment of the multidrug-resistant phenotype. Here we show that: i) Sorcin is overexpressed in several tumors and cancer cell lines, in particular resistant to chemotherapeutic drugs; ii) Sorcin binds doxorubicin, paclitaxel, vinblastine and cisplatin, acting as a drug "sink" and hamperi ng doxorubicin nuclear uptake, thus allowing cell survival; iii) Sorcin overexpression increases resistance to doxorubicin, whereas its inhibition decreases ABCB1 expression and activity, decreasing drug efflux.
In conclusion, therefore, sorcin is a key determinant of drug resistance in cancer.
Not only P-glycoprotein: Amplification of the ABCB1-containing chromosome region 7q21 confers multidrug resistance upon cancer cells by coordinated overexpression of an assortment of resistance-related proteins. Genovese I, Ilari A, Assaraf YG, Fazi F, Colotti G. Drug Resist Updat. 2017; 32:23-46. doi:10.1016/j.drup.2017.10.003.