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Organ-Specific Cancer Metabolism and Its Potential for Therapy
Ilaria Elia1,2, Roberta Schmieder1,2, Stefan Christen1,2
1Vesalius Research Center, VIB, 3000, Leuven, Belgium.
Abstract:
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.
Insights
Cancer cell metabolism is not singular but dictated by tumor requirements, varying by cancer type. Targeting these diverse metabolic needs offers promising therapeutic strategies for cancer treatment.
Area of Science:
- Oncology
- Cancer Biology
- Metabolic Pathways
Background:
- Targeting cancer metabolism is a key strategy in tumor therapy.
- Cancer cell metabolism is highly adaptable and not uniform across all cancers.
- Tumor metabolism is influenced by tissue of origin, genetic factors, signaling pathways, and the microenvironment.
Purpose of the Study:
- To explore the diversity of cancer metabolism.
- To analyze how genetic, signaling, and environmental factors shape tumor metabolism.
- To assess the therapeutic potential of targeting cancer metabolism.
Main Methods:
- Comparative analysis of cancer metabolism across different cancer types.
- Discussion of metabolic behaviors in triple-negative and estrogen receptor-positive breast cancer, early- and late-stage prostate cancer, and liver cancer.
- Evaluation of therapeutic concepts like metabolic normalization and depletion.
Main Results:
- Cancer metabolism is not a single entity but is tailored to tumor-specific requirements.
- Distinct metabolic profiles, including Warburg and reverse Warburg metabolism, are observed in different cancers.
- Despite variations, unique metabolic strategies support the oncogenic phenotype in each cancer type.
Conclusions:
- Understanding the heterogeneity of cancer metabolism is crucial for effective therapy.
- Metabolic normalization and depletion represent viable therapeutic avenues.
- Tailoring metabolic interventions to specific cancer types holds significant therapeutic promise.
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