Autophagy as a modulator and target in prostate cancer.
Autophagy as a modulator and target in prostate cancer.
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DOI：
10.1038/nrurol.2014.196
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发表时间：
2014-09
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--
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自噬，或“自我进食”，是一种适应性过程，有助于细胞应对代谢，毒性，甚至感染性压力。虽然自噬的适应能力通常是有益的，但自噬也可以促进癌细胞中营养利用的提高和生长特性的改善。此外，自噬可以在治疗干预的背景下促进更大的细胞稳健性。这已被证明是晚期前列腺癌的情况，其中临床前数据在很大程度上支持自噬促进疾病进展和治疗抗性。值得注意的是，雄激素剥夺治疗，紫杉烷为基础的化疗，靶向激酶抑制，营养限制都诱导显着的细胞窘迫。自噬随后通过核心代谢调节信号级联（即AMPK、PI3K和mTOR）上调，并建立更有利的生长和营养条件。目前的研究还表明，当自噬机制被抑制时，可以获得更大的细胞杀伤和肿瘤反应性。在这篇综述中，我们将涵盖与自噬改变相关的当前前列腺癌治疗;支持自噬调节的数据，并强调前列腺癌模型中发生的改变;最后，研究支持辅助自噬调节与当前前列腺癌治疗范例。
Autophagy, or “self eating,” is an adaptive process that helps cells cope with metabolic, toxic, and even infectious stressors. While the adaptive capability of autophagy is generally beneficial, autophagy can also facilitate enhanced nutrient utilization and improved growth characteristics in cancer cells. Moreover, autophagy can promote greater cellular robustness in the context of therapeutic intervention. This has proven to be the case in advanced prostate cancer, where preclinical data largely supports that autophagy facilitates both disease progression and therapeutic resistance. Notably, androgen deprivation therapy, taxane-based chemotherapy, targeted kinase inhibition, and nutrient restriction all induce significant cellular distress. Autophagy is subsequently up-regulated through core metabolic regulatory signaling cascades (i.e. AMPK, PI3K, and mTOR), and more favorable growth and nutrient conditions are established. Current research also demonstrates that when the autophagic machinery is inhibited, greater cell killing and tumor responsiveness can be obtained. In this review, we will cover current prostate cancer treatments associated with alterations in autophagy; data supporting autophagic modulation with added emphasis on alterations occurring within prostate cancer models; and finally, research supporting adjuvant autophagic modulation with current prostate cancer treatment paradigms.
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