The hallmarks of cancer metabolism: still emerging

Pavlova, Natalya N.; Zhu, Jiajun; Thompson, Craig B.

doi:10.1016/j.cmet.2022.01.007

Cited by 1,418Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerCancer and biochemical research

The hallmarks of cancer metabolism: still emerging

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Pavlova, Natalya N., Zhu, Jiajun, Thompson, Craig B.·2022·Cell Metabolism

DOI 10.1016/j.cmet.2022.01.007PMC PMC8891094

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Abstract

Metabolism of cancer cells is geared toward biomass production and proliferation. Since the metabolic resources within the local tissue are finite, this can lead to nutrient depletion and accumulation of metabolic waste. To maintain growth in these conditions, cancer cells employ a variety of metabolic adaptations, the nature of which is collectively determined by the physiology of their cell of origin, the identity of transforming lesions, and the tissue in which cancer cells reside. Furthermore, select metabolites not only serve as substrates for energy and biomass generation, but can also regulate gene and protein expression and influence the behavior of non-transformed cells in the tumor vicinity. As they grow and metastasize, tumors can also affect and be affected by the nutrient distribution within the body. In this hallmark update, recent advances are incorporated into a conceptual framework that may help guide further research efforts in exploring cancer cell metabolism.

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Cancer cells primarily use glucose, fatty acids, and amino acids to meet their biosynthetic needs.
“In other words, cancer cells primarily use glucose, fatty acids, and amino acids to meet their biosynthetic needs [49–52].”
From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [50]
The Introduction’s “Deregulated uptake of glucose and amino acids” section describes glucose-derived carbon and glutamine supporting biosynthesis. “Use of central carbon metabolism to support biosynthesis” describes fatty acids chiefly as products of lipogenesis, while “Use of opportunistic modes of nutrient acquisition” describes extracellular lipid uptake under particular conditions. The copy therefore does not support grouping fatty acids with glucose and amino acids as nutrients cancer cells primarily use for biosynthesis. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Although glycolysis produces less ATP per glucose than OXPHOS, it maintains bioenergetic flux during oxygen deprivation and generates intermediates for biosynthetic pathways such as the pentose phosphate pathway and fatty acid or amino acid synthesis.
“While glycolysis is less efficient than oxidative phosphorylation (OXPHOS) in generating ATP per molecule of glucose, the switch to glycolysis enables maintained bioenergetic flux during oxygen deprivation, and generates glycolytic intermediates that can be diverted into biosynthetic processes such as the pentose phosphate pathway (PPP) for nucleotide biosynthesis or fatty acid and amino acid”
From The HIF Axes in Cancer - Angiogenesis, Metabolism and Immune-Modulation (2025) · cites this paper as [39]
The two hallmarks exhibit commonalities but also differences or antagonisms between aging-associated deregulated nutrient sensing and cancer-associated deregulation of cellular energy metabolism.
“Both hallmarks exhibit clear commonalities, but there are also some differences or even antagonisms between aging-associated deregulated nutrient sensing and cancer-associated deregulation of cellular energy metabolism.[204][205][206]”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [204]
Several chemical intermediates of the TCA cycle serve as critical precursors for biosynthetic reactions.
“However, several chemical intermediates of the TCA cycle also serve as critical precursors for biosynthetic reactions, which we will discuss in detail later (5, 6).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [6]

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Authors: Pavlova, N. N., Zhu, J., & Thompson, C. B.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
Center for Life Sciences (CN)
Corresponding author: Thompson, Craig B.
ORCID: Pavlova, Natalya N.
Zhu, Jiajun
Thompson, Craig B.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2022-03
Volume: 34
Issue: 3
Pages: 355-377
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2022.01.007
PMC: PMC8891094
OpenAlex: W4220798004
Cited by: 1,418
References: 216
Citations by year: 2026: 314 · 2025: 392 · 2024: 386 · 2023: 241 · 2022: 85
FWCI: 33.89
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 365 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (P30 CA008748, R01 CA248355-01)
Agios Pharmaceuticals
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
Keywords: cancer metabolism, cancer hallmarks, tumor cell proliferation, biomass production, nutrient depletion, metabolic waste accumulation, metabolic adaptation, tumor microenvironment, metastasis
MeSH terms: Nutrients, Energy Metabolism, Humans, Neoplasms

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The hallmarks of cancer metabolism: still emerging

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