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Published on: February 2, 2024
Metabolism remodeling in pancreatic ductal adenocarcinoma
Jin-Tao Li1, Yi-Ping Wang1, Miao Yin1
1Fudan University Shanghai Cancer Center and Cancer Metabolism Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of death of patients with malignant cancers by 2030. Current options of PDAC treatment are limited and the five-year survival rate is less than 8%, leading to an urgent need to explore innovatively therapeutic strategies. PDAC cells exhibit extensively reprogrammed metabolism to meet their energetic and biomass demands under extremely harsh conditions. The metabolic changes are closely linked to signaling triggered by activation of oncogenes like KRAS as well as inactivation of tumor suppressors. Furthermore, tumor microenvironmental factors including extensive desmoplastic stroma reaction result in series of metabolism remodeling to facilitate PDAC development. In this review, we focus on the dysregulation of metabolism in PDAC and its surrounding microenvironment to explore potential metabolic targets in PDAC therapy.
Insights
Pancreatic cancer (PDAC) metabolism is reprogrammed by oncogenes and the tumor microenvironment. Targeting these metabolic changes offers innovative therapeutic strategies for this deadly disease.
Area of Science:
- Oncology
- Cancer Metabolism
- Molecular Biology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with poor prognosis.
- Current treatments for PDAC are limited, with a five-year survival rate below 8%.
- PDAC exhibits significant metabolic reprogramming to support its growth in a harsh tumor microenvironment.
Purpose of the Study:
- To review metabolic dysregulation in PDAC.
- To explore the role of the tumor microenvironment in PDAC metabolism.
- To identify potential metabolic targets for novel PDAC therapies.
Main Methods:
- Literature review of studies on PDAC metabolism.
- Analysis of metabolic alterations driven by oncogenes (e.g., KRAS) and tumor suppressors.
- Investigation of microenvironmental factors influencing PDAC metabolism.
Main Results:
- PDAC cells extensively reprogram metabolism to meet high energy and biomass demands.
- Metabolic changes are linked to oncogene activation (e.g., KRAS) and tumor suppressor inactivation.
- The desmoplastic stroma reaction in the tumor microenvironment significantly remodels PDAC metabolism.
Conclusions:
- Metabolic reprogramming is a hallmark of PDAC.
- Targeting metabolic pathways presents a promising therapeutic avenue for PDAC.
- Understanding the interplay between PDAC cells and their microenvironment is crucial for developing effective treatments.
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