Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management

Abstract

Pancreatic cancer (PC) begins within the organ of the pancreas, which produces digestive enzymes, and is one of the formidable cancers for which appropriate treatment strategies are urgently needed. Autophagy occurs in the many chambers of PC tissue, including cancer cells, cancer-related fibroblasts, and immune cells, and can be fine-tuned by various promotive and suppressive signals. Consequently, the impacts of autophagy on pancreatic carcinogenesis and progression depend greatly on its stage and conditions. Autophagy inhibits the progress of preneoplastic damage during the initial phase. However, autophagy encourages tumor formation during the development phase. Several studies have reported that both a tumor-promoting and a tumor-suppressing function of autophagy in cancer that is likely cell-type dependent. However, autophagy is dispensable for pancreatic ductal adenocarcinoma (PDAC) growth, and clinical trials with autophagy inhibitors, either alone or in combination with other therapies, have had limited success. Autophagy’s dual mode of action makes it therapeutically challenging despite autophagy inhibitors providing increased longevity in medical studies, highlighting the need for a more rigorous review of current findings and more precise targeting strategies. Indeed, the role of autophagy in PC is complicated, and numerous factors must be considered when transitioning from bench to bedside. In this review, we summarize the evidence for the tumorigenic and protective role of autophagy in PC tumorigenesis and describe recent advances in the understanding of how autophagy may be regulated and controlled in PDAC.

Clinical Evaluation of the Pancreatic Cancer Microenvironment: Opportunities and Challenges

“…This example is but one of many complex roles for autophagy that have been described in PDAC initiation and development (reviewed in [169]). Clinical trials of autophagy inhibitors in PDAC have yet to show efficacy; one phase II trial found that hydroxychloroquine monotherapy reduced autophagy but had negligible efficacy in patients with previously treated metastatic PDAC [170].…”

Coronavirus (SARS-CoV-2) Infection and Pathogenicity: The Roles of Cell Death and Autophagy

“…In order to create DMVs derived from ER membranes, SARS-CoV-2 can divert autophagy flux. This creates niches for immune evasion and viral RNA replication [44].…”

Potential Therapeutic Implication of Herbal Medicine in Mitochondria-Mediated Oxidative Stress-Related Liver Diseases

“…ROS secreted from mitochondria is removed by cell antioxidant systems, and various cell components are oxidatively damaged due to hydroxyl radical (•OH) formation [ 12 , 13 ]. Low and moderate level of ROS is a critical mediator of metabolism and inflammation, but an excessive level of ROS contributes to apoptosis or autophagy containing H 2 O 2 − sensitive pathways, respectively [ 14 , 15 , 16 , 17 ]. Notably, excessive amounts of ROS are highly toxic to cells.…”