Recent evidence suggests that genetic and epigenetic mechanisms might be associated with acquired resistance to cancer therapies.The aim of this study was to assess the association of genome-wide genetic and epigeneti...Recent evidence suggests that genetic and epigenetic mechanisms might be associated with acquired resistance to cancer therapies.The aim of this study was to assess the association of genome-wide genetic and epigenetic alterations with the response to anti-HER2 agents in HER2-positive breast cancer patients.PubMed was screened for articles published until March 2021 on observational studies investigating the association of genome-wide genetic and epigenetic alterations,measured in breast cancer tissues or blood,with the response to targeted treatment in HER2-positive breast cancer patients.Sixteen studies were included in the review along with ours,in which we compared the genome-wide DNA methylation pattern in breast tumor tissues of patients who acquired resistance to treatment (case group, n = 6) to that of patients who did not develop resistance (control group, n =6). Among genes identified as differentially methylated between the breast cancer tissue of cases and controls, oneof them, PRKACA, was also reported as differentially expressed in two studies included in the review. Althoughincluded studies were heterogeneous in terms of methodology and study population, our review suggests thatgenes of the PI3K pathway may play an important role in developing resistance to anti-HER2 agents in breastcancer patients. Genome-wide genetic and epigenetic alterations measured in breast cancer tissue or blood mightbe promising markers of resistance to anti-HER2 agents in HER2-positive breast cancer patients. Further studiesare needed to confirm these data.展开更多
文摘Recent evidence suggests that genetic and epigenetic mechanisms might be associated with acquired resistance to cancer therapies.The aim of this study was to assess the association of genome-wide genetic and epigenetic alterations with the response to anti-HER2 agents in HER2-positive breast cancer patients.PubMed was screened for articles published until March 2021 on observational studies investigating the association of genome-wide genetic and epigenetic alterations,measured in breast cancer tissues or blood,with the response to targeted treatment in HER2-positive breast cancer patients.Sixteen studies were included in the review along with ours,in which we compared the genome-wide DNA methylation pattern in breast tumor tissues of patients who acquired resistance to treatment (case group, n = 6) to that of patients who did not develop resistance (control group, n =6). Among genes identified as differentially methylated between the breast cancer tissue of cases and controls, oneof them, PRKACA, was also reported as differentially expressed in two studies included in the review. Althoughincluded studies were heterogeneous in terms of methodology and study population, our review suggests thatgenes of the PI3K pathway may play an important role in developing resistance to anti-HER2 agents in breastcancer patients. Genome-wide genetic and epigenetic alterations measured in breast cancer tissue or blood mightbe promising markers of resistance to anti-HER2 agents in HER2-positive breast cancer patients. Further studiesare needed to confirm these data.
