2020年美国临床肿瘤学会(Amecican Society of Clinical Oncology,ASCO)年会于5月末隆重召开,对于激素受体(hormonal receptor,HR)阳性乳腺癌内分泌治疗方案在早期和晚期患者治疗的进展均有重磅报道。其中早期HR+乳腺癌内分泌治疗进展...2020年美国临床肿瘤学会(Amecican Society of Clinical Oncology,ASCO)年会于5月末隆重召开,对于激素受体(hormonal receptor,HR)阳性乳腺癌内分泌治疗方案在早期和晚期患者治疗的进展均有重磅报道。其中早期HR+乳腺癌内分泌治疗进展主要集中于内分泌治疗在新辅助治疗中的探索,包括氟维司群单药以及氟维司群联合阿那曲唑在新辅助内分泌治疗疗效的研究。晚期HR+乳腺癌内分泌治疗进展集中于靶向治疗联合内分泌治疗的疗效研究和精细化管理,包括磷脂酰肌醇3-激酶(phosphatidylinositol3-kinase,PI 3K)抑制剂联合内分泌治疗、细胞周期依赖激酶(cyclin D-dependent kinase,CDK)4/6抑制剂联合内分泌治疗的深入探索,涉及对内分泌耐药、内脏转移等人群的疗效和安全性分析。本研究分别对早期及晚期HR+乳腺癌内分泌治疗的重要进展进行报道和解读。展开更多
Breast cancer,one of the most frequent cancer types,is a leading cause of death in women worldwide.Estrogen receptor(ER)αis a nuclear hormone receptor that plays key roles in mammary gland development and breast canc...Breast cancer,one of the most frequent cancer types,is a leading cause of death in women worldwide.Estrogen receptor(ER)αis a nuclear hormone receptor that plays key roles in mammary gland development and breast cancer.About 75%of breast cancer cases are diagnosed as ER-positive;however,nearly half of these cancers are either intrinsically or inherently resistant to the current anti-estrogen therapies.Recent studies have identified an ER coactivator,Mediator Subunit 1(MED1),as a unique,tissue-specific cofactor that mediates breast cancer metastasis and treatment resistance.MED1 is overexpressed in over 50%of human breast cancer cases and co-amplifies with another important breast cancer gene,receptor tyrosine kinase HER2.Clinically,MED1 expression highly correlates with poor disease-free survival of breast cancer patients,and recent studies have reported an increased frequency of MED1 mutations in the circulating tumor cells of patients after treatment.In this review,we discuss the biochemical characterization of MED1 and its associated MED1/Mediator complex,its crosstalk with HER2 in anti-estrogen resistance,breast cancer stem cell formation,and metastasis both in vitro and in vivo.Furthermore,we elaborate on the current advancements in targeting MED1 using state-of-the-art RNA nanotechnology and discuss the future perspectives as well.展开更多
文摘2020年美国临床肿瘤学会(Amecican Society of Clinical Oncology,ASCO)年会于5月末隆重召开,对于激素受体(hormonal receptor,HR)阳性乳腺癌内分泌治疗方案在早期和晚期患者治疗的进展均有重磅报道。其中早期HR+乳腺癌内分泌治疗进展主要集中于内分泌治疗在新辅助治疗中的探索,包括氟维司群单药以及氟维司群联合阿那曲唑在新辅助内分泌治疗疗效的研究。晚期HR+乳腺癌内分泌治疗进展集中于靶向治疗联合内分泌治疗的疗效研究和精细化管理,包括磷脂酰肌醇3-激酶(phosphatidylinositol3-kinase,PI 3K)抑制剂联合内分泌治疗、细胞周期依赖激酶(cyclin D-dependent kinase,CDK)4/6抑制剂联合内分泌治疗的深入探索,涉及对内分泌耐药、内脏转移等人群的疗效和安全性分析。本研究分别对早期及晚期HR+乳腺癌内分泌治疗的重要进展进行报道和解读。
基金Project supported by the National Cancer Institute(No.R01CA197865),the Ride Cincinnati Awardthe National Center for Advancing Translation Science of the National Institutes of Health(No.UL1TR001425),USA
文摘Breast cancer,one of the most frequent cancer types,is a leading cause of death in women worldwide.Estrogen receptor(ER)αis a nuclear hormone receptor that plays key roles in mammary gland development and breast cancer.About 75%of breast cancer cases are diagnosed as ER-positive;however,nearly half of these cancers are either intrinsically or inherently resistant to the current anti-estrogen therapies.Recent studies have identified an ER coactivator,Mediator Subunit 1(MED1),as a unique,tissue-specific cofactor that mediates breast cancer metastasis and treatment resistance.MED1 is overexpressed in over 50%of human breast cancer cases and co-amplifies with another important breast cancer gene,receptor tyrosine kinase HER2.Clinically,MED1 expression highly correlates with poor disease-free survival of breast cancer patients,and recent studies have reported an increased frequency of MED1 mutations in the circulating tumor cells of patients after treatment.In this review,we discuss the biochemical characterization of MED1 and its associated MED1/Mediator complex,its crosstalk with HER2 in anti-estrogen resistance,breast cancer stem cell formation,and metastasis both in vitro and in vivo.Furthermore,we elaborate on the current advancements in targeting MED1 using state-of-the-art RNA nanotechnology and discuss the future perspectives as well.
