自噬与前列腺癌

自噬(autophagy)是真核细胞通过溶酶体对其自身结构进行降解的一个生物学过程,其在细胞的生存、生长、分化以及维持内环境稳定等方面发挥着重要的作用。在肿瘤的发生和发展过程中,自噬的调控机制比较复杂,且具有两面性。在肿瘤发生的早期,自噬可以通过清除受损细胞器、促进蛋白分解代谢而发挥抑制肿瘤的作用。然而,在肿瘤进展中,在缺氧或营养受限的状态下,肿瘤细胞可通过自噬的作用降解、循环再利用细胞内物质,促进自身存活。前列腺癌是男性生殖系统中最常见的恶性肿瘤。近年来的研究表明,前列腺癌的发生和发展与自噬密切相关。因此,本文就自噬在前列腺癌中的调控机制进行综述,以期为前列腺癌的治疗提供一些新的线索和途径。     

自噬在肿瘤治疗中的作用

自噬是细胞内物质再利用的重要过程,日渐增多的证据表明自噬在肿瘤的发生、发展和抗肿瘤治疗过程中发挥着重要作用。本文就自噬的分子生物学基础及自噬在肿瘤治疗中的作用做一综述。     

自噬及其与结直肠癌的发生和治疗

自噬是细胞通过降解自身的蛋白质及细胞器并循环利用降解产物以维持细胞生存的,过度自噬可导致细胞自噬性死亡.近年来研究发现,自噬在结直肠癌发生、发展及治疗中有重要作用,但其作用机制和对放化疗疗效的影响仍存在争议.     

自噬调节因子Ambra1在肿瘤中的研究进展

Ambra1作为自噬调节因子，在自噬体的形成过程中扮演了重要角色，其介导的自噬参与细胞增殖、分化、发育、凋亡等生物学过程，与肿瘤进展密切相关。目前研究发现Ambra1介导的自噬对肿瘤细胞具有保护作用，但亦可能通过调控其他信号通路发挥抑制肿瘤作用。本文就自噬调节因子Ambra1在肿瘤中的研究进展作一综述。     

自噬在肿瘤中的双重作用

自噬是一种溶酶体降解途径, 通过对细胞内变性蛋白或受损细胞器进行降解, 以维持细胞内物质循环及代谢调节的稳定。自噬是一把双刃剑, 在肿瘤微环境中, 自噬既能在不利环境中提高肿瘤细胞对应激的耐受能力, 维持其生存, 又能在肿瘤发展的不同阶段抑制其产生和转移, 甚至成为某些凋亡缺陷肿瘤细胞的死亡途径。此外, 自噬的双重作用还表现在癌症治疗过程中。因此, 深入探讨自噬在肿瘤中的双重作用有助于为肿瘤防治提供新思路。      

自噬在肺癌发生发展中的研究进展

肺癌是临床常见的恶性肿瘤之一,具有发展速度快、恶性程度高等特点。自噬是细胞的代谢过程,可作为肺癌治疗的靶点。一方面,自噬可通过维持基因稳定并清除促癌因子、参与免疫反应、促进肿瘤细胞程序性死亡等途径抑制肺癌的发生。另一方面,自噬又能促进肿瘤细胞生长,为其生长提供充足的营养,并对化疗药物产生一定的抵抗。自噬与肺癌的关系较为密切,其在肺癌发生、发展、治疗等过程中发挥着重要作用。本文对自噬在肺癌发生发展中的研究进展进行综述。     

天然草药—癌症治疗中的潜在自噬诱导剂

自噬是一种维持细胞内稳态的重要代谢过程。近年来研究发现,自噬与肿瘤的发生发展密切相关,参与调控肿瘤的形成、增殖、转移以及能量代谢等过程。并且自噬在肿瘤的发生发展中发挥着不同的作用,它能抑制早期肿瘤的生成,促进晚期肿瘤的发展。目前,自噬已成为肿瘤药物靶向研究中的一个新热点。许多草药,包括中草药,已作为现行药物的补充和替代药物、保健品和营养品,以减轻癌症治疗中化疗药物的毒副反应。此外,许多草药及天然产物均可通过诱导自噬,进而导致细胞衰老、凋亡非依赖性细胞死亡途径或补体介导的细胞凋亡途径的激活,最终发挥着抗肿瘤作用。据此,本文将回顾分析天然自噬诱导剂在癌症治疗中的潜在作用机制。同时,我们着重探讨白藜芦醇、姜黄素和16-羟基克罗烷-3,13-二烯-15,16-内酯这三种天然化合物作为候选自噬诱导剂在癌症治疗中的研究进展,旨在为研发靶向自噬的新型抗肿瘤药物提供方向。     

自噬在三阴性乳腺癌中的研究进展

细胞自噬是真核细胞对细胞内物质进行周转的重要过程,对于维持细胞内环境的稳定和营养物质的循环利用至关重要。自噬在肿瘤细胞的治疗中起到双重的作用,既可引起癌细胞自噬性死亡,提高细胞对放化疗的敏感性,有助于肿瘤的治疗,又可在不良环境中保护细胞,增加癌细胞的耐药性及提高癌细胞的生存率。在目前的研究报道中,调控自噬活性的信号分子将可能成为三阴性乳腺癌潜在的诊治靶点。笔者针对细胞自噬与三阴性乳腺癌的增殖、迁移、侵袭等功能,放射治疗、药物治疗及预后等方面的研究进展进行综述。     

自噬与肿瘤转移的相关性研究

自噬是一种在正常细胞和肿瘤细胞中普遍存在的生命现象。肿瘤细胞通过转移定植到远隔器官,必须适应严峻恶劣的微环境。在这一系列转移事件中,自噬发挥了双重作用。研究证明自噬能抑制原发性肿瘤的形成,但关于自噬如何影响肿瘤转移尚不清楚,本文将对自噬的概念及生物学特性、肿瘤转移的基本过程、自噬在肿瘤转移过程中的作用机制以及自噬在肿瘤治疗中的应用做一综述。     

去势抵抗性前列腺癌化疗耐药机制的研究进展

前列腺癌的发病率和死亡率逐年上升,去势治疗是中晚期前列腺癌的最主要治疗方法,但去势抵抗性前列腺癌为临床治疗难点,化疗虽为后续主要治疗手段,但易出现耐药。最新研究表明,去势抵抗性前列腺癌患者化疗后再使用抗雄激素药物能提高总生存率。本文就近年来去势抵抗性前列腺癌化疗耐药相关机制做一综述,探讨雄激素受体、自噬、JAK/STAT3信号通路在去势抵抗性前列腺癌发生化疗耐药过程中所发挥的调控作用。     

宫颈癌细胞自噬与Wnt/β-catenin信号通路关系的研究进展

自噬是真核细胞内发生的一种高度保守的自我降解机制,宫颈癌的肿瘤细胞自噬是肿瘤进展的重要因素。自噬作用的下调与宫颈细胞HPV感染、宫颈癌的产生存在紧密联系。Wnt信号通路在宫颈癌细胞的自我更新和分化的调控中扮演重要角色,越来越多的研究证明Wnt信号通路表达的激活及β-catenin的异常表达与宫颈癌密切相关。宫颈癌细胞自噬与Wnt/β-catenin信号通路之间存在一定关系并相互作用,影响着癌症的发生发展。本文就宫颈癌细胞自噬与Wnt/β-catenin信号通路关系综述如下。     

Targeting autophagy in cancer

Autophagy is a conserved, self‐degradation system that is critical for maintaining cellular homeostasis during stress conditions. Dysregulated autophagy has implications in health and disease. Specifically, in cancer, autophagy plays a dichotomous role by inhibiting tumor initiation but supporting tumor progression. Early results from clinical trials that repurposed hydroxychloroquine for cancer have suggested that autophagy inhibition may be a promising approach for advanced cancers. In this review of the literature, the authors present fundamental advances in the biology of autophagy, approaches to targeting autophagy, the preclinical rationale and clinical experience with hydroxychloroquine in cancer clinical trials, the potential role of autophagy in tumor immunity, and recent developments in next‐generation autophagy inhibitors that have clinical potential. Autophagy is a promising target for drug development in cancer. Cancer 2018. © 2018 American Cancer Society.     

Targeting Tyrosine Kinases and Autophagy in Prostate Cancer

Tyrosine kinases play significant roles in tumor progression and therapy resistance. Inhibitors of tyrosine kinases are on the forefront of targeted therapy. For prostate cancer, tyrosine kinases play an additional role in the development of castration-resistant disease state, the most troubling aspect of prostate cancinogenesis which presently defies any effective treatment. Among the 30 or so tyrosine kinases expressed in a typical prostate cancer cell, nearly one third of them have been implicated in prostate carcinogenesis. Interestingly, most of them channel signals through a trio of non-receptor tyrosine kinases, Src/Etk/FAK, referred here as Src tyrosine kinase complex. This complex has been shown to play a significant role in the aberrant activation of androgen receptor (AR) mediated by growth factors (e.g., epidermal growth factor (EGF)), cytokines (interleukin (IL)-6), chemokines (IL-8), and neurokines (gastrin-releasing peptide). These factors are induced and released from the prostate cancer to the stromal cells upon androgen withdrawal. The Src kinase complex has the ability to phosphorylate androgen receptor, resulting in the nuclear translocation and stabilization of un-liganded androgen receptor. Indeed, tyrosine kinase inhibitors targeting Src can inhibit androgen-independent growth of prostate cancer cells in vitro and in preclinical xenograft model. While effective in inducing growth arrest and inhibiting metastasis of castration-resistant tumors, Src inhibitors rarely induce a significant level of apoptosis. This is also reflected by the general ineffectiveness of tyrosine kinase inhibitors as monotherapy in clinical trials. One of the underlying causes of apoptosis resistance is "autophagy," which is induced by tyrosine kinase inhibitors and by androgen withdrawal. Autophagy is a self-digesting process to regenerate energy by removal of long-lived proteins and retired organelles to provide a survival mechanism to cells encountering stresses. Excessive autophagy, sometimes, could lead to type II programmed cell death. We demonstrated that autophagy blockade sensitizes prostate cancer cells toward Src tyrosine kinase inhibitor. Thus, a combination therapy based on Src tyrosine kinase inhibitor and autophagy modulator deserves further attention as a potential treatment for relapsed prostate cancer.     

内质网-自噬途径在肿瘤耐药中的研究现状

自噬在肿瘤治疗中扮演着双重角色.多数化疗药物能够通过激活内质网应激来诱导肿瘤细胞自噬,过度激活的自噬能够造成肿瘤细胞凋亡,发挥抗肿瘤作用.自噬对肿瘤细胞又具有保护作用,它能够通过对破损细胞器的降解再利用,维持肿瘤细胞活性,降低对化学药物的敏感性.因此,促进或抑制自噬的调节剂联合化疗药物在肿瘤治疗中将具有发展潜力.     

Chitosan nanoparticle-mediated delivery of miRNA-34a decreases prostate tumor growth in the bone and its expression induces non-canonical autophagy

While several new therapies are FDA-approved for bone-metastatic prostate cancer (PCa), patient survival has only improved marginally. Here, we report that chitosan nanoparticle-mediated delivery of miR-34a, a tumor suppressive microRNA that downregulates multiple gene products involved in PCa progression and metastasis, inhibited prostate tumor growth and preserved bone integrity in a xenograft model representative of established PCa bone metastasis. Expression of miR-34a induced apoptosis in PCa cells, and, in accord with downregulation of targets associated with PCa growth, including MET and Axl and c-Myc, also induced a form of non-canonical autophagy that is independent of Beclin-1, ATG4, ATG5 and ATG7. MiR-34a-induced autophagy is anti-proliferative in prostate cancer cells, as blocking apoptosis still resulted in growth inhibition of tumor cells. Thus, combined effects of autophagy and apoptosis are responsible for miR-34a-mediated prostate tumor growth inhibition, and have translational impact, as this non-canonical form of autophagy is tumor inhibitory. Together, these results provide a new understanding of the biological effects of miR-34a and highlight the clinical potential for miR-34a delivery as a treatment for bone metastatic prostate cancer.     

自噬在胃癌中的研究进展

近年来，自噬在胃癌中的作用得到了广泛的关注，自噬犹如一把“双刃剑”在肿瘤发展过程中扮演重要的双面角色，对肿瘤的发展既有抑制作用，又有促进作用，本文对自噬抑制胃癌早期的形成以及促进中晚期胃癌的药物抗性等最新研究进展进行介绍。探讨细胞自噬与胃癌的关系，有助于深入了解胃癌的发生发展以及预后等一系列问题，希望为胃癌的早期诊断和诊治提供新的治疗途径。     

43th ISOBM Annual Congress of International Society of Oncology and BioMarkers,September 1-6, 2016 Chicago,USA

Nowadays, heat shock protein 90 (Hsp90), a highly conserved molecular chaperone, has become the target of antitumor drugs as a result of its close relationship with the occurrence and development, biological behavior, and prognosis of a tumor. Autophagy has attracted big attention recently for its paradoxical roles in cell survival and cell death, especially in the pathogenesis and treatment of cancer. Moreover, it has been verified that Hsp90 plays a role in autophagy via regulating the stability and activity of signaling proteins, and some Hsp90 inhibitors can induce autophagy. However, the underlying mechanisms for these important processes have not been clarified so far. In this study, we focus on the roles of Hsp90 in the regulation of autophagy, such as toll-like receptor (TLR)-mediated autophagy, Ulk1-mediated mitophagy, and chaperone-mediated autophagy (CMA). The roles of Hsp90 inhibitors in cancer therapy will also be elucidated.     

自噬在恶性肿瘤治疗中的进展及影像学应用前景

自噬是在营养缺乏条件下维持细胞代谢的主要途径。这使其成为肿瘤研究的新热点,调控自噬信号通路的机制已经很明确,越来越多的研究发现机体细胞自噬活性变化对肿瘤治疗的效果具有巨大影响。但缺乏能够重复比较或靶向定位自噬活性的测量技术。正电子示踪剂PET等影像手段通过将相关自噬的信号通路蛋白标记放射性核素进行显像似乎具有解决这些问题的潜力。在本文中,我们综述自噬在肿瘤治疗中的应用,并展望医学影像技术协助自噬治疗肿瘤的前景。     

Autophagy in breast cancer and its implications for therapy

Autophagy is an evolutionarily conserved process of cellular self-digestion that serves as a mechanism to clear damaged organelles and recycle nutrients. Since autophagy can promote cell survival as well as cell death, it has been linked to different human pathologies, including cancer. Although mono-allelic deletion of autophagy-related gene BECN1 in breast tumors originally indicated a tumor suppressive role for autophagy in breast cancer, the intense research during the last decade suggests a role for autophagy in tumor progression. It is now recognized that tumor cells often utilize autophagy to survive various stresses, such as oncogene-induced transformation, hypoxia, endoplasmic reticulum (ER) stress and extracellular matrix detachment. Induction of autophagy by tumor cells may also contribute to tumor dormancy and resistance to anticancer therapies, thus making autophagy inhibitors promising drug candidates for breast cancer treatment. The scientific endeavors continue to define a precise role for autophagy in breast cancer. In this article, we review the current literature on the role of autophagy during the development and progression of breast cancer, and discuss the potential of autophagy modulators for breast cancer treatment.