Frontiers in Pharmacology (Nov 2021)
Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma
- Alexander G. Raufi,
- Alexander G. Raufi,
- Alexander G. Raufi,
- Alexander G. Raufi,
- Nicholas R. Liguori,
- Nicholas R. Liguori,
- Lindsey Carlsen,
- Lindsey Carlsen,
- Lindsey Carlsen,
- Lindsey Carlsen,
- Cassandra Parker,
- Cassandra Parker,
- Liz Hernandez Borrero,
- Liz Hernandez Borrero,
- Shengliang Zhang,
- Shengliang Zhang,
- Shengliang Zhang,
- Shengliang Zhang,
- Xiaobing Tian,
- Xiaobing Tian,
- Xiaobing Tian,
- Xiaobing Tian,
- Anna Louie,
- Anna Louie,
- Lanlan Zhou,
- Lanlan Zhou,
- Lanlan Zhou,
- Lanlan Zhou,
- Attila A. Seyhan,
- Attila A. Seyhan,
- Attila A. Seyhan,
- Attila A. Seyhan,
- Wafik S. El-Deiry,
- Wafik S. El-Deiry,
- Wafik S. El-Deiry,
- Wafik S. El-Deiry,
- Wafik S. El-Deiry,
- Wafik S. El-Deiry
Affiliations
- Alexander G. Raufi
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Alexander G. Raufi
- Hematology/Oncology Division, Department of Medicine, Lifespan Health System and Brown University, Providence, RI, United States
- Alexander G. Raufi
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI, United States
- Alexander G. Raufi
- Cancer Center at Brown University, Providence, RI, United States
- Nicholas R. Liguori
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Nicholas R. Liguori
- Temple University, Lewis Katz School of Medicine, Philadelphia, PA, United States
- Lindsey Carlsen
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Lindsey Carlsen
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI, United States
- Lindsey Carlsen
- Cancer Center at Brown University, Providence, RI, United States
- Lindsey Carlsen
- Pathobiology Graduate Program, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Cassandra Parker
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Cassandra Parker
- Department of Surgery, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Liz Hernandez Borrero
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Liz Hernandez Borrero
- Pathobiology Graduate Program, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Shengliang Zhang
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Shengliang Zhang
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI, United States
- Shengliang Zhang
- Cancer Center at Brown University, Providence, RI, United States
- Shengliang Zhang
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Xiaobing Tian
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Xiaobing Tian
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI, United States
- Xiaobing Tian
- Cancer Center at Brown University, Providence, RI, United States
- Xiaobing Tian
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Anna Louie
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Anna Louie
- Department of Surgery, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Lanlan Zhou
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Lanlan Zhou
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI, United States
- Lanlan Zhou
- Cancer Center at Brown University, Providence, RI, United States
- Lanlan Zhou
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Attila A. Seyhan
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Attila A. Seyhan
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI, United States
- Attila A. Seyhan
- Cancer Center at Brown University, Providence, RI, United States
- Attila A. Seyhan
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Wafik S. El-Deiry
- Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Wafik S. El-Deiry
- Hematology/Oncology Division, Department of Medicine, Lifespan Health System and Brown University, Providence, RI, United States
- Wafik S. El-Deiry
- Joint Program in Cancer Biology, Lifespan Health System and Brown University, Providence, RI, United States
- Wafik S. El-Deiry
- Cancer Center at Brown University, Providence, RI, United States
- Wafik S. El-Deiry
- Pathobiology Graduate Program, Warren Alpert Medical School, Brown University, Providence, RI, United States
- Wafik S. El-Deiry
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States
- DOI
- https://doi.org/10.3389/fphar.2021.751568
- Journal volume & issue
-
Vol. 12
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by early metastasis, late detection, and poor prognosis. Progress towards effective therapy has been slow despite significant efforts. Novel treatment approaches are desperately needed and autophagy, an evolutionary conserved process through which proteins and organelles are recycled for use as alternative energy sources, may represent one such target. Although incompletely understood, there is growing evidence suggesting that autophagy may play a role in PDAC carcinogenesis, metastasis, and survival. Early clinical trials involving autophagy inhibiting agents, either alone or in combination with chemotherapy, have been disappointing. Recently, evidence has demonstrated synergy between the MAPK pathway and autophagy inhibitors in PDAC, suggesting a promising therapeutic intervention. In addition, novel agents, such as ONC212, have preclinical activity in pancreatic cancer, in part through autophagy inhibition. We discuss autophagy in PDAC tumorigenesis, metabolism, modulation of the immune response, and preclinical and clinical data with selected autophagy modulators as therapeutics.
Keywords
