自噬调节与肿瘤治疗

自噬是一个细胞质成分被双层膜的囊泡包裹并与溶酶体融合降解的过程.肿瘤细胞利用自噬过程存活于代谢应激下,因此推测自噬抑制剂在肿瘤治疗中具有临床应用价值.与此相矛盾的是在人类乳腺肿瘤、卵巢肿瘤、前列腺肿瘤中,重要的自噬基因beclinl等位性丢失发生很频繁,表明自噬的受损促使肿瘤的发生.与自噬缺陷和对代谢应激损伤耐受有关的...

Autophagy modulation in cancer therapy

Autophagy is a process by which cytoplasmic components are sequestered in double membrane vesicles and degraded upon fusion with lysosomal compartments. Autophagy is utilized by tumor cells to survive metabolic stress and as such autophagy inhibitors are predicted to have clinical value in the setting of cancer therapy. Paradoxically, allelic loss of the essential autophagy gene beclin1 is found with high frequency in human breast, ovarian and prostate cancers, suggesting that impaired autophagy promotes cancer. Probable causes of cancer associated with defects in autophagy and impaired tolerance to stress include enhanced cell death resulting in an inflammatory response and cytokine production, and also genome damage. This suggests that autophagy inducers would also be valuable in the setting of cancer prevention to limit cellular genome damage, cell death and inflammation. As autophagy is a major component of the cellular stress response, modulating the autophagy pathway is a promising new area in cancer prevention and therapy.