Breast cancer(BC)is the second most common cause of cancer-related deaths and the most frequently diagnosed cancer in females.Among breast cancer types,HER2-positive breast cancer occurs in nearly 20%of human breast c...Breast cancer(BC)is the second most common cause of cancer-related deaths and the most frequently diagnosed cancer in females.Among breast cancer types,HER2-positive breast cancer occurs in nearly 20%of human breast cancers and is associated with increased aggressiveness,poor prognosis,and shortened overall survival.HER2+breast cancer is currently managed with multidisciplinary treatment strategies including surgery,radiation,chemotherapy,and targeted therapy.Drug resistance remains a continuing challenge,especially to targeted therapy utilizing monoclonal antibodies and tyrosine kinase inhibitors.This review discusses some of the recent molecular mechanisms that are involved in the development of resistance to Her2-targeted therapies including the PI3K/Akt/mTOR pathway,IGF-IR,Src,c-MET,the PP2A family,CD36,p27^(kip1),and miRNAs.展开更多
An estimated 30,000 men in the United States will die of metastatic prostate cancer(PCa)each year due to the development of therapy resistance,most notably resistance to second-generation antiandrogen enzalutamide.The...An estimated 30,000 men in the United States will die of metastatic prostate cancer(PCa)each year due to the development of therapy resistance,most notably resistance to second-generation antiandrogen enzalutamide.The vast majority of PCa is driven by the androgen receptor(AR).Enzalutamide is an AR antagonist,which extends patient survival and is widely used in the clinic for the treatment of castration-resistant prostate cancer(CRPC);however,many patients will have primary or develop acquired resistance and continue to progress.Characterization of the molecular mechanisms of enzalutamide resistance provides insight into potentially efficacious therapies for enzalutamide-resistant CRPC(ER-CRPC).Understanding these mechanisms is critical for the identification of biomarkers predictive of therapy resistance and the development of therapeutic strategies to target ER-CRPC.展开更多
文摘Breast cancer(BC)is the second most common cause of cancer-related deaths and the most frequently diagnosed cancer in females.Among breast cancer types,HER2-positive breast cancer occurs in nearly 20%of human breast cancers and is associated with increased aggressiveness,poor prognosis,and shortened overall survival.HER2+breast cancer is currently managed with multidisciplinary treatment strategies including surgery,radiation,chemotherapy,and targeted therapy.Drug resistance remains a continuing challenge,especially to targeted therapy utilizing monoclonal antibodies and tyrosine kinase inhibitors.This review discusses some of the recent molecular mechanisms that are involved in the development of resistance to Her2-targeted therapies including the PI3K/Akt/mTOR pathway,IGF-IR,Src,c-MET,the PP2A family,CD36,p27^(kip1),and miRNAs.
基金This work was supported by the Department of Defense(W81XWH017-1-0674)the Prostate Cancer Foundation(18CHAL16)as well as support from the Cole Foundation and the Wilson Foundation.
文摘An estimated 30,000 men in the United States will die of metastatic prostate cancer(PCa)each year due to the development of therapy resistance,most notably resistance to second-generation antiandrogen enzalutamide.The vast majority of PCa is driven by the androgen receptor(AR).Enzalutamide is an AR antagonist,which extends patient survival and is widely used in the clinic for the treatment of castration-resistant prostate cancer(CRPC);however,many patients will have primary or develop acquired resistance and continue to progress.Characterization of the molecular mechanisms of enzalutamide resistance provides insight into potentially efficacious therapies for enzalutamide-resistant CRPC(ER-CRPC).Understanding these mechanisms is critical for the identification of biomarkers predictive of therapy resistance and the development of therapeutic strategies to target ER-CRPC.
