05)。联合MK-2206可明显降低阿霉素对两种细胞IC50值,但MCF-7/ADR细胞的降低程度明显大于MCF-7细胞(P0.05)。单独MK-2206处理后,MCF-7细胞p-(Thr308)Akt蛋白表达明显下调(P0.05);MCF-7/ADR细胞以上两种蛋白的表达均明显下调(均P
子宫内膜癌是常见的女性恶性生殖道肿瘤,其晚期或复发患者的预后仍然较差。近些年新出现的靶向治疗已成为晚期或复发子宫内膜癌的重要治疗手段。PI3K/Akt/mTOR信号通路在子宫内膜癌的发生发展过程中起着重要的调节作用,抑制该通路有效位点的靶向治疗可能提高晚期或复发子宫内膜癌的治疗效果。但目前针对该信号通路的药物研究仍处于初步阶段,仍需要更多的临床试验加以明确疗效。
脑胶质瘤病(GC)是一种病因未明的罕见颅内原发性肿瘤,呈弥漫性、浸润性生长,但保存脑组织的大体结构是其主要特征;其临床症状复杂多样,影像学表现特异性不强,只有通过病理学检查方能确诊。由于GC的特性,手术、化疗和放疗的疗效均不理想,预后不佳。本文着重阐述了GC的诊断及治疗的新进展,供同道参考。
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KRX-0401体外 estrogen receptor(ER) pathway plays a critical role in breast cancer development and progression. Endocrine therapy targeting estrogen action is the most important systemic therapy for ER positive breast cancer. However its efficacy is limited by intrinsic and acquired resistance. Mechanisms responsible for endocrine resistance include deregulation of the ER pathway itself, including loss of ER expression, posttranslational modification of ER, deregulation of ER coactivators; increased receptor tyrosine kinase signaling leading to activation of various intracellular pathways involved in signal

Inhibitor Library transduction, proliferation and cell survival, including growth factor receptor tyrosine kinases human epidermal growth factor receptor-2, epidermal growth factor receptor, PI3K/AKT/mammalian target of rapamycin(m TOR), Mitogen activated kinase(MAPK)/ERK, fibroblast growth factor receptor, insulin-like growth factor-1 receptor; alterations in cell cycle and apoptotic machinery; Epigenetic modificationincluding dysregulation of DNA methylation, histone modification, and nucleosome remodeling; and altered expression of specific micro RNAs. Functional genomics has helped us identify a catalog of genetic and epigenetic alterations 一般 that may be exploited as potential therapeutic targets and biomarkers

of response. New treatment combinations targeting ER and such oncogenic signaling pathways which block the crosstalk between these pathways have been proven effective in preclinical models. Results of recent clinical studies suggest that subsets of patients benefit from the combination of inhibitor targeting certain oncogenic signaling pathway with endocrine therapy. Especially, inhibition of the m TOR signaling pathway, a key component implicated in mediating multiple signaling cascades, offers a promising approach to restore sensitivity to endocrine therapy in breast cancer. We systematically reviewed important publications cited in Pub Med, recent abstracts from ASCO annual meetings and San Antonio Breast Cancer Symposium, and relevant trials registered at Clinical Trials.gov. We present the molecular mechanisms contributing to endocrine resistance, in particular focusing on the biological rationale for the clinical development of novel targeted agents in endocrine resistant breast cancer.