Colorectal cancer heterogeneity : integrating and exploiting therapy- and microenvironment-mediated metabolic adaptation to tackle disease progression
(2024)
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Details
- Authors
Richiardone, Elena 
- Supervisors
- Corbet, Cyril
- Abstract
- Colorectal cancer (CRC) ranks among the most prevalent and deadly malignancies worldwide. Therapy-induced stress and microenvironmental constraints compel cancer cells to reprogram their metabolism to support survival and proliferation. This doctoral thesis explores the metabolic changes in CRC cells chronically exposed either to anti-EGFR targeted therapy or to acidic pH conditions. This work sheds light on the pivotal roles for several metabolic pathways, including lactate and serine metabolism as well as mitochondrial respiration, as adaptive phenotypic changes to sustain CRC cell aggressiveness. Additionally, an in-depth analysis of phenotypic remodeling in acidosis-adapted CRC cells identified a novel gene signature related to tumor acidosis. Together, these findings provide valuable insights into the metabolic reprogramming of aggressive CRC cells, offering a foundation for the development of novel therapeutic strategies.
- Affiliations
Citations
Richiardone, E. (2024). Colorectal cancer heterogeneity : integrating and exploiting therapy- and microenvironment-mediated metabolic adaptation to tackle disease progression.