Exploiting pancreatic cancer metabolism: challenges and opportunities
Tumor and its immune microenvironment metabolism emerge as critical hallmarks that should be considered in the design and application of novel therapeutic drugs in pancreatic cancer.The heterogeneity of pancreatic cancer metabolism, and the different metabolic behavior between primary tumors and met...
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| Published in: | Trends in molecular medicine 2024-04 |
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| Main Authors: | , , , , |
| Format: | Article |
| Language: | eng |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Tumor and its immune microenvironment metabolism emerge as critical hallmarks that should be considered in the design and application of novel therapeutic drugs in pancreatic cancer.The heterogeneity of pancreatic cancer metabolism, and the different metabolic behavior between primary tumors and metastasis, pose a challenge to the effectiveness of existing treatments.The synthesis of polyamines using glutamine as a main source is emerging as a key feature of pancreatic cancer.The targeting of tumor metabolism may help in reprograming the tumor immune microenvironment (TIME) and promoting the response to immunotherapy.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive form of pancreatic cancer, known for its challenging diagnosis and limited treatment options. The focus on metabolic reprogramming as a key factor in tumor initiation, progression, and therapy resistance has gained prominence. In this review we focus on the impact of metabolic changes on the interplay among stromal, immune, and tumor cells, as glutamine and branched-chain amino acids (BCAAs) emerge as pivotal players in modulating immune cell functions and tumor growth. We also discuss ongoing clinical trials that explore metabolic modulation for PDAC, targeting mitochondrial metabolism, asparagine and glutamine addiction, and autophagy inhibition. Overcoming challenges in understanding nutrient effects on immune–stromal–tumor interactions holds promise for innovative therapeutic strategies.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive form of pancreatic cancer, known for its challenging diagnosis and limited treatment options. The focus on metabolic reprogramming as a key factor in tumor initiation, progression, and therapy resistance has gained prominence. In this review we focus on the impact of metabolic changes on the interplay among stromal, immune, and tumor cells, as glutamine and branched-chain amino acids (BCAAs) emerge as pivotal players in modulating immune cell functions and tumor growth. We also discuss ongoing clinical trials that explore metabolic modulation for PDAC, targeting mitochondrial metabolism, asparagine and glutamine addiction, and autophagy inhibition. Overcoming challenges in understanding nutrient effects on immune–stromal–tumor interactions holds promise for innovative therapeutic strategies. |
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| ISSN: | 1471-4914 1471-499X |