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Review
. 2024 Jan 29;13(1):10.
doi: 10.1186/s40164-024-00482-x.

Cancer metabolism and carcinogenesis

Jianqiang Yang  1 , Chloe Shay  2 , Nabil F Saba  1 , Yong Teng  3   4
Affiliations
Review

Cancer metabolism and carcinogenesis

Jianqiang Yang et al. Exp Hematol Oncol. .

Abstract

Metabolic reprogramming is an emerging hallmark of cancer cells, enabling them to meet increased nutrient and energy demands while withstanding the challenging microenvironment. Cancer cells can switch their metabolic pathways, allowing them to adapt to different microenvironments and therapeutic interventions. This refers to metabolic heterogeneity, in which different cell populations use different metabolic pathways to sustain their survival and proliferation and impact their response to conventional cancer therapies. Thus, targeting cancer metabolic heterogeneity represents an innovative therapeutic avenue with the potential to overcome treatment resistance and improve therapeutic outcomes. This review discusses the metabolic patterns of different cancer cell populations and developmental stages, summarizes the molecular mechanisms involved in the intricate interactions within cancer metabolism, and highlights the clinical potential of targeting metabolic vulnerabilities as a promising therapeutic regimen. We aim to unravel the complex of metabolic characteristics and develop personalized treatment approaches to address distinct metabolic traits, ultimately enhancing patient outcomes.

Keywords: Heterogeneous treatment effect; Metabolic exchange and integration; Metabolic heterogeneity; Metabolic patterns and regulation; Tumor heterogeneity.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Metabolic patterns and their continuous transition in cancer cells. These metabolic patterns can transition from one to another according to different triggers and requirements in cancer cells. (A) Schematic representation of glycolytic metabolic phenotype. Cancer cells in the glycolytic metabolic pattern take up high levels of glucose and produce high levels of lactate to meet energy and synthesis demands. (B) Schematic representation of OXPHOS metabolic phenotype. Cancer cells have a better “burn efficiency” by relying on high mitochondrial function and consuming more oxygen. (C) Schematic representation of combined metabolic phenotype. Cancer cells in the metabolic pattern have high plasticity and characteristics of high glycolysis and mitochondrial metabolism
Fig. 2
Fig. 2
Glutaminolysis at different stages of the metabolism. Glutamate is converted to the TCA cycle intermediate α-KG and the corresponding amino acid. The newly formed citrate exits the mitochondria where it is used to synthesize fatty acids and amino acids, transfer glutamate to the cytoplasm, and synthesize GSH, which is critical for maintaining redox homeostasis and protecting cells from oxidative stress. a broad upregulation of biosynthetic pathways characterizes proliferative and metastatic metabolism by glutamine. (A) In quiescent metabolism, glutamine metabolism is maintained at a low level. (B) In the proliferative stage, glutamine consumption has increased and more GSH is needed to counteract oxidative stress. (C) When cancer cells transform to the metastatic stage, more lipids and nucleotides are synthesized to adapt to the synthetic needs
Fig. 3
Fig. 3
Metabolic switch during cancer cell invasion and metastasis. The metabolic pattern of cancer cells changes in response to various factors within the TME. (A) During preparation for invasion, there is an increase in ROS, a decrease in ATP synthesis, and activation of FAO to compensate for ATP synthesis. (B) During the metastatic process, increased TCA cycle and reduced ROS by CPT1A lead to increased ATP synthesis. (C) When cancer cells metastasize to target organs, there is a shift in the energy patterns that is influenced by the specific organ and its microenvironment
Fig. 4
Fig. 4
The factors driving metastatic dynamics. The metabolic dynamics of cancer cells are extremely complex and are influenced by multiple factors including genetic alterations, immune responses, epigenetic modifications, therapeutic interventions, and adaptations within the TME. The metabolic profiles of cancer cells are altered in response to single or multiple factors [, –, , , –145]
Fig. 5
Fig. 5
The main metabolic pathways for three key nutrients in cancer cells, along with their typical inhibitors. These inhibitors can be directed to impede the functioning of the pathways by targeting the relevant transporters and directly inhibiting the corresponding rate-limiting enzymes
See this image and copyright information in PMC

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