Organ-Specific Cancer Metabolism and Its Potential for Therapy.
Targeting cancer metabolism has the potential to lead to major advances in tumor therapy. Numerous promising metabolic drug targets have been identified. Yet, it has emerged that there is no singular metabolism that defines the oncogenic state of the cell. Rather, the metabolism of cancer cells is a function of the requirements of a tumor. Hence, the tissue of origin, the (epi)genetic drivers, the aberrant signaling, and the microenvironment all together define these metabolic requirements. In this chapter we discuss in light of (epi)genetic, signaling, and environmental factors the diversity in cancer metabolism based on triple-negative and estrogen receptor-positive breast cancer, early- and late-stage prostate cancer, and liver cancer. These types of cancer all display distinct and partially opposing metabolic behaviors (e.g., Warburg versus reverse Warburg metabolism). Yet, for each of the cancers, their distinct metabolism supports the oncogenic phenotype. Finally, we will assess the therapeutic potential of metabolism based on the concepts of metabolic normalization and metabolic depletion.
Vesalius Research Center, VIB, 3000, Leuven, Belgium.|Department of Oncology, KU Leuven, 3000, Leuven, Belgium.
Ilaria
I
Elia
Vesalius Research Center, VIB, 3000, Leuven, Belgium.|Department of Oncology, KU Leuven, 3000, Leuven, Belgium.
Roberta
R
Schmieder
Vesalius Research Center, VIB, 3000, Leuven, Belgium.|Department of Oncology, KU Leuven, 3000, Leuven, Belgium.
Stefan
S
Christen
Vesalius Research Center, VIB, 3000, Leuven, Belgium. sarah-maria.fendt@vib-kuleuven.be.|Department of Oncology, KU Leuven, 3000, Leuven, Belgium. sarah-maria.fendt@vib-kuleuven.be.
Sarah-Maria
SM
Fendt
D001943:Breast Neoplasms / Q000378:metabolism; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000378:metabolism; D059016:Tumor Microenvironment
Cancer metabolism; Epigenetic drivers; Estrogen receptor-positive breast cancer; Fatty acid metabolism; Genetic drivers; Gluconeogenesis; Glucose metabolism; Glutamine metabolism; Liver cancer; Metabolic depletion; Metabolic normalization; Metabolic therapy; Microenvironment; Mixed Warburg effect; Prostate cancer; Reverse Warburg effect; Serine metabolism; Tissue-specific metabolism; Triple-negative breast cancer; Warburg effect