However, as previously mentioned multiple chemotherapeutic agents can lead to the release of HMGB1, which leads to the development of drug resistance, and this is no different in bladder cancer.HMGB1 is passively released in response to gemcitabine, which attenuates the anticancer effect of gemcitabine by mediating an increase in autophagy (73). This evidence concerns the gene HMGB1 and urinary bladder carcinoma.