Contrast effects of autophagy in the treatment of bladder cancer

Abstract

Bladder cancer is a disease that negatively affects patients’ quality of life, but treatment options have remained unchanged for a long time. Although promising results have been achieved with current bladder cancer treatments, cancer recurrence, progression, and therapy resistance are the most severe problems preventing the efficiency of bladder cancer treatments. Autophagy refers to an evolutionarily conserved catabolic process in which proteins, damaged organelles, and cytoplasmic components are degraded by lysosomal enzymes. Autophagy regulates the therapeutic response to the chemotherapy drugs, thus determining the effect of therapy on cancer cells. Autophagy is a stress-induced cell survival mechanism and its excessive stimulation can cause resistance of tumor cells to therapeutic agents. Depending on the conditions, an increase in autophagy may cause treatment resistance or autophagic cell death, and it is related to important anti-cancer mechanisms, such as apoptosis. Therefore, understanding the roles of autophagy under different conditions is important for designing effective anti-cancer agents. The dual role of autophagy in cancer has attracted considerable attention in respect of bladder cancer treatment. In this review, we summarize the basic characteristics of autophagy, including its mechanisms, regulation, and functions, and we present examples from current studies concerning the dual role of autophagy in bladder cancer progression and therapy. Impact statement Autophagy acts as an intracellular recycling system. Infection and mitochondrial damage, maintaining cellular homeostasis, orchestrating nutrient stress, hypoxia, and oxidative stress are some of the physiological roles associated with autophagy. Autophagy has also context-dependent roles in cancer. Autophagy has a significant impact on tumor initiation and promotion, with both tumor-suppressive and tumor-promoting roles. Unfortunately, conventional systemic chemotherapy for cancer therapy has been reported to have primary limitations such as chemo-resistance of targeted cells. The cytoprotective role of autophagy has been postulated as one of the causes of this resistance. Hence, combination therapy using autophagy inhibitors has recently started to emerge as a noteworthy strategy in the treatment of cancer. Therefore, targeting the autophagy pathways may be a potential therapeutic strategy for addressing cancer progression or therapy resistance in the near future. This review will provide a novel insight to understanding the paradoxical roles of autophagy in tumor suppression and tumor promotion.

Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cells

“…Autophagy is commonly exploited by cancer cells to fulfill the high metabolic demands of tumors. However, the effects of autophagy on cancer cell progression are context-dependent and may in some cases restrict growth [ 31 ]. Hence, modulation of autophagy represents an enticing anticancer strategy.…”

The Regulating Effect of Autophagy-Related MiRNAs in Kidney, Bladder, and Prostate Cancer

“…At present, in the diagnosis and treatment of kidney, bladder, and prostate cancer, both the classical autophagy inhibitors, such as chloroquine and hydroxychloroquine, and the preclinical development of more autophagy-related experimental compounds are determined by the duality of autophagy. It is necessary for us to determine the factors that cause the condition-dependent behavior of autophagy, study different genes and signal pathways, and identify molecular markers to understand how autophagy works at the molecular level, so as to be more helpful to tumor targets towards treatment [ 88 , 89 ]. As mentioned above, the key role of miRNA in tumors is undoubted.…”

Long Noncoding RNA H19 Derived from M2 Tumor-Associated Macrophages Promotes Bladder Cell Autophagy via Stabilizing ULK1

“…Recently, autophagy has been proved to play critical roles in almost all the diseases especially in cancers [ 4 , 5 ]. During BC development and tumorigenesis, autophagy was found to act as a double-edged sword in respect of molecular mechanisms of bladder cancer [ 6 ].…”