Bortnik Svetlana, Gorski Sharon M
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
Interdisciplinary Oncology Program, University of British Columbia, Vancouver, BC V5Z 1L3, Canada.
Int J Mol Sci. 2017 Jul 11;18(7):1496. doi: 10.3390/ijms18071496.
Autophagy, a lysosome-mediated intracellular degradation and recycling pathway, plays multiple context-dependent roles in tumorigenesis and treatment resistance. Encouraging results from various preclinical studies have led to the initiation of numerous clinical trials with the intention of targeting autophagy in various cancers. Accumulating knowledge of the particular mechanisms and players involved in different steps of autophagy regulation led to the ongoing discovery of small molecule inhibitors designed to disrupt this highly orchestrated process. However, the development of validated autophagy-related biomarkers, essential for rational selection of patients entering clinical trials involving autophagy inhibitors, is lagging behind. One possible source of biomarkers for this purpose is the autophagy machinery itself. In this review, we address the recent trends, challenges and advances in the assessment of the biomarker potential of clinically relevant autophagy proteins in human cancers.
自噬是一种由溶酶体介导的细胞内降解和再循环途径,在肿瘤发生和治疗耐药性中发挥多种依赖于背景的作用。各种临床前研究取得的令人鼓舞的结果已促使开展了众多临床试验,旨在针对各种癌症中的自噬进行靶向治疗。对自噬调节不同步骤中涉及的特定机制和参与者的认识不断积累,导致不断发现旨在破坏这一高度协调过程的小分子抑制剂。然而,用于合理选择进入涉及自噬抑制剂的临床试验的患者的经过验证的自噬相关生物标志物的开发却滞后了。为此目的,生物标志物的一个可能来源是自噬机制本身。在本综述中,我们阐述了评估人类癌症中临床相关自噬蛋白的生物标志物潜力的最新趋势、挑战和进展。