Cellular resistance to anthracyclines

Remission of human breast cancer xenografts on therapy with humanized monoclonal antibody to HER-2 receptor and DNA-reactive drugs

“…Although the molecular consequences of cisplatin (Chu, 1994) and doxorubicin (Sawyer et al, 1988;Purewal and Liehr, 1993;Cutts et al, 1994;Nielsen et al, 1996) therapy and antireceptor antibody-receptor interactions (Drebin et al, 1988;Sarup et al, 1991;Scott et al, 1991) are incompletely understood, the present evidence is consistent with independent reports which show that antibodies to the HER-2 receptor not only elicit growth inhibition on their own (Drebin et al, 1988;Hudziak et al, 1989;Chazin et al, 1992) but can modulate the sensitivity to DNA-reactive drugs (Hancock et al, 1991;Shepard et al, 1991;Pietras et al, 1994). Doxorubicin is generally considered to act as a DNA-intercalating agent, but recent reports suggest that anthracyclines might also indirectly promote covalent modi®cation of DNA and possibly induce adduct formation (Sawyer et al, 1988;Purewal and Liehr, 1993;Cutts et al, 1994).…”

“…DNA repair is well known to play an important role in the recovery of cells from the toxicity of DNAreactive drugs (Zhen et al, 1992;Nielsen et al, 1996), and changes in cisplatin-induced DNA repair have been reported to occur in HER-2-overexpressing cells after treatment with antibodies to HER-2 receptor (Pietras et al, 1994;Arteaga et al, 1994). To further evaluate the role of DNA repair as an explanation for the therapeutic advantage of antireceptor antibody and DNA-reactive drugs, we measured unscheduled DNA synthesis induced by cisplatin and doxorubicin in MCF-7 cells (Figure 8).…”

“…Although anthracyclines are not generally considered to be DNA-damaging agents, recent data suggests these agents may elicit indirect covalent modi®cations of DNA in mammary tissue (Purewal and Liehr, 1993;Nielsen et al, 1996). To evaluate the potential eect of doxorubicin on DNA repair pathways, unscheduled DNA synthesis after doxorubicin in MCF-7 cells was also measured.…”

Autophagy protects breast cancer cells from epirubicin-induced apoptosis and facilitates epirubicin-resistance development

“…It is established that MDR (multidrug resistance) is the main mechanism of EPI resistance. 3,4 In addition, EPI eliminates cancer cells via inducing apoptosis, whereas one of the important features of cancer cells is evading apoptosis through a variety of mechanisms. 5,6 Thus, damage of apoptotic machinery in cancer cells also results in resistance to EPI.…”

Concise prediction models of anticancer efficacy of 8 drugs using expression data from 12 selected genes

“…17,24,29 TUBB and TYMS are targets of DOX, toxoids and 5-FU, respectively; and expression of TOP2A may have a part in the sensitivity of topoisomerase I inhibitors due to its compensatory mechanisms for loss of function of topoisomerase I. 18,22,23,27,28 We believe our approach is one of the most practical ways available to identify better prediction markers of drug response.…”