ABSTRACT
Autophagy, an evolutionarily conserved lysosomal degradation process, has drawn an increasing amount of attention in recent years for its role in a variety of human diseases, such as cancer. Notably, autophagy plays an important role in regulating several survival and death signaling pathways that determine cell fate in cancer. To date, substantial evidence has demonstrated that some key autophagic mediators, such as autophagy-related genes (ATGs), PI3K, mTOR, p53, and Beclin-1, may play crucial roles in modulating autophagic activity in cancer initiation and progression. Because autophagy-modulating agents such as rapamycin and chloroquine have already been used clinically to treat cancer, it is conceivable that targeting autophagic pathways may provide a new opportunity for discovery and development of more novel cancer therapeutics. With a deeper understanding of the regulatory mechanisms governing autophagy, we will have a better opportunity to facilitate the exploitation of autophagy as a target for therapeutic intervention in cancer. This review discusses the current status of targeting autophagic pathways as a potential cancer therapy.
Subject(s)
Humans , Antibiotics, Antineoplastic , Therapeutic Uses , Apoptosis Regulatory Proteins , Metabolism , Autophagy , Genetics , Beclin-1 , Chloroquine , Therapeutic Uses , Drug Discovery , Membrane Proteins , Metabolism , Molecular Targeted Therapy , Neoplasms , Metabolism , Pathology , Therapeutics , Phosphatidylinositol 3-Kinases , Metabolism , Signal Transduction , Sirolimus , Therapeutic Uses , TOR Serine-Threonine Kinases , Metabolism , Tumor Suppressor Protein p53 , MetabolismABSTRACT
Autophagy, a cellular process of "self-eating" by which intracellular components are degraded within the lysosome, is an evolutionarily conserved response to various stresses. Autophagy is associated with numerous patho-physiological conditions, and dysregulation of autophagy contributes to the pathogenesis of a variety of human diseases including cancer. Depending on context, activation of autophagy may promote either cell survival or death, two major events that determine pathological process of many illnesses. Importantly, the activity of autophagy is often associated with apoptosis, another critical cellular process determining cellular fate. A better understanding of biology of autophagy and its implication in human health and disorder, as well as the relationship between autophagy and apoptosis, has the potential of facilitating the development of autophagy-based therapeutic interventions for human diseases such as cancer.
Subject(s)
Humans , Apoptosis , Autophagy , Cell Death , Cell Survival , Neoplasms , PathologyABSTRACT
<p><b>OBJECTIVE</b>To provide a summary of the relationship between the eEF-2/eEF-2 kinase pathway and each phase of malignant neoplasms. The speci?c importance of this relationship in understanding and treating cancer was also explored.</p><p><b>DATA SOURCES</b>The data used in this review were mainly obtained from the articles listed in HighWire and PubMed in English. The search terms were "eEF-2 kinase", "oncogenesis", and "tumor progression".</p><p><b>STUDY SELECTION</b>This review relates the observation that the overexpression of eEF-2 kinase is seen in cancer, and highlights that it has emerged as promoting the development of many malignant phenotypes when unregulated. This includes increasing the replicative potential of cells, angiogenesis, invasion and metastasis, and evasion of apoptosis.</p><p><b>RESULTS</b>eEF-2 kinase is a structurally and functionally unique protein kinase. The increased activity of this protein in cancer cells is a protective mechanism to allow tumor growth and evolution, and resist cell death through the eEF-2/eEF-2 kinase pathway, but it also makes a potential target for therapy.</p><p><b>CONCLUSION</b>eEF-2 kinase fills critical niches in the life of a cancer cell and the eEF-2/eEF-2 kinase pathway is a key biochemical sensor.</p>