A group of cancer researchers at University of Colorado School of Medicine showed in a series of elegant experimental set-up that there is a functional reciprocal relationship between lysosome activity and metastasis that allows chloroquine and other inhibitors of lysosome function, such as bafilomycin A1, to preferentially kill human metastatic bladder cancer cells by targeting autophagy-independent lysosome functions. They also demonstrated that chloroquine treatment of bladder cancer cells and subsequent acquisition of resistance to this therapy lead to altered gene expression programs that drive a less aggressive and metastatic phenotype via up-regulation of inhibitor of DNA binding 4, also known as ID4.
This work suggest that there is an intimate reciprocal relationship between metastatic ability and lysosome function and that targeting the lysosome itself, rather than autophagy specifically, may provide an effective therapy in patients with metastasis.
This work also has clinical implications as to how ID4 expression could be used as a predictive and prognostic biomarker for chloroquine sensitivity and metastasis in patients with bladder cancer.
http://www.pnas.org/content/early/2018/08/15/1706526115
This work suggest that there is an intimate reciprocal relationship between metastatic ability and lysosome function and that targeting the lysosome itself, rather than autophagy specifically, may provide an effective therapy in patients with metastasis.
This work also has clinical implications as to how ID4 expression could be used as a predictive and prognostic biomarker for chloroquine sensitivity and metastasis in patients with bladder cancer.
http://www.pnas.org/content/early/2018/08/15/1706526115
