Postdoctoral associate, Indian institute of science, Bangalore


How does the phenotypic diversity among the tumor heterogeneity contribute in drug resistance

Drug treatment induces phenotypic switch and stemness in acquiring resistance


The conventional anti-cancer therapy is becoming a challenge to abolish tumor due to the development of drug resistance. Tumor cells acquire resistance due to intra-tumor heterogeneity imposed by epithelial to mesenchymal transition. The drugs which target epithelial cells may fail to target mesenchymal and the intermediate phenotypes due to which the cancer cells acquire drug resistance. This concept provoked us to understand the phenotypic diversity among the tumor heterogeneity which might lead to drug resistance. Treatment of breast cancer cell lines MCF7 and MDA MB 231 with Doxorubicin showed a loss of epithelial markers and gain of mesenchymal markers, and vice versa in MDA MB 231 cells, thereby shifting to an intermediate phenotype. Furthermore, Doxorubicin treatment of MDA MB 231-nanog stable cells led to an increase in nanog positive cells. Thus, our current data suggests that the anti-cancer therapy induces cancer cells to undergo a phenotypic switch and increases the stemness property which might be responsible to gain resistance. Identification of the critical regulators of the phenotypic switch by phosphoproteomics analysis may help us investigate the possible mechanisms underlying the anti-cancer drug resistance. Previous reports also suggest that conventional therapies fail to eliminate cancer stem cells thereby letting the tumor relapse. Our present study might contribute in understanding the possible mechanism of anti-cancer drug resistance and hence might help improve the clinical therapy.