Curated Papers > Recent high-impact research on "tumor microenvironment" (IF ≥ 30, last 5 years)

Metabolic Codependencies in the Tumor Microenvironment.

Literature Information

DOI	10.1158/2159-8290.CD-20-1211
PMID	33504580
Journal	Cancer discovery
Impact Factor	33.3
JCR Quartile	Q1
Publication Year	2021
Times Cited	174
Keywords	Metabolic reprogramming, Tumor microenvironment, Signal transduction
Literature Type	Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review
ISSN	2159-8274
Pages	1067-1081
Issue	11(5)
Authors	Prasenjit Dey, Alec C Kimmelman, Ronald A DePinho

TL;DR

This review discusses how metabolic reprogramming in cancer cells is influenced by both intrinsic mechanisms, driven by oncogenic alterations, and extrinsic factors from the tumor microenvironment, which together enhance metabolic regulation crucial for tumor growth and survival. Understanding these converging signals is significant for developing targeted therapies that consider a cancer's specific genotype and microenvironment.

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Metabolic reprogramming · Tumor microenvironment · Signal transduction

Abstract

Metabolic reprogramming enables cancer cell growth, proliferation, and survival. This reprogramming is driven by the combined actions of oncogenic alterations in cancer cells and host cell factors acting on cancer cells in the tumor microenvironment. Cancer cell-intrinsic mechanisms activate signal transduction components that either directly enhance metabolic enzyme activity or upregulate transcription factors that in turn increase expression of metabolic regulators. Extrinsic signaling mechanisms involve host-derived factors that further promote and amplify metabolic reprogramming in cancer cells. This review describes intrinsic and extrinsic mechanisms driving cancer metabolism in the tumor microenvironment and how such mechanisms may be targeted therapeutically. SIGNIFICANCE: Cancer cell metabolic reprogramming is a consequence of the converging signals originating from both intrinsic and extrinsic factors. Intrinsic signaling maintains the baseline metabolic state, whereas extrinsic signals fine-tune the metabolic processes based on the availability of metabolites and the requirements of the cells. Therefore, successful targeting of metabolic pathways will require a nuanced approach based on the cancer's genotype, tumor microenvironment composition, and tissue location.

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Primary Questions Addressed

1. How do specific oncogenic alterations in cancer cells influence metabolic reprogramming in the tumor microenvironment?
2. What role do host-derived factors play in modulating the metabolic pathways of cancer cells?
3. Can you elaborate on the therapeutic strategies that target both intrinsic and extrinsic metabolic mechanisms in cancer treatment?
4. How does the composition of the tumor microenvironment affect the metabolic dependencies of different cancer types?
5. What are the implications of metabolic reprogramming for the development of resistance to cancer therapies?

Key Findings

Research Background and Objectives

Cancer cells undergo metabolic reprogramming to support their growth, proliferation, and survival. This reprogramming is influenced by both intrinsic oncogenic alterations within cancer cells and extrinsic factors from the tumor microenvironment. The aim of this review is to elucidate the mechanisms—both intrinsic and extrinsic—that drive cancer metabolism and to explore potential therapeutic targets.

Main Methods/Materials/Experimental Design

The review synthesizes findings from various studies to present a comprehensive overview of the mechanisms involved in cancer metabolic reprogramming. The following flowchart illustrates the key components involved in this process:

Key Results and Findings

1. Intrinsic Mechanisms: Oncogenic alterations activate signaling pathways that enhance metabolic enzyme activities and upregulate transcription factors. This leads to an increase in metabolic regulators that sustain cancer cell metabolism.
2. Extrinsic Mechanisms: Host-derived factors in the tumor microenvironment contribute to metabolic reprogramming by fine-tuning metabolic processes according to the availability of nutrients and the specific demands of cancer cells.
3. Converging Signals: Both intrinsic and extrinsic factors converge to shape the metabolic landscape of cancer cells, allowing them to adapt to changing environments.

Main Conclusions/Significance/Innovativeness

The review highlights the complexity of cancer metabolism, emphasizing that effective therapeutic strategies must consider both intrinsic and extrinsic factors. Understanding these mechanisms can lead to more tailored approaches for targeting metabolic pathways in cancer treatment, taking into account the specific genotype of the cancer, the composition of the tumor microenvironment, and the tissue location.

Research Limitations and Future Directions

• Limitations: The review primarily synthesizes existing literature without presenting new experimental data. It may not encompass all possible intrinsic and extrinsic factors affecting cancer metabolism.
• Future Directions: Further research is needed to explore the detailed interactions between intrinsic and extrinsic signals in various cancer types. Investigating how these pathways can be selectively targeted for therapeutic benefit will be crucial for advancing cancer treatment strategies. Additionally, understanding the dynamic nature of the tumor microenvironment and its impact on metabolic reprogramming will be essential for developing effective interventions.

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Literatures Citing This Work

1. Lessons from Cancer Metabolism for Pulmonary Arterial Hypertension and Fibrosis. - SeungHye Han;Navdeep S Chandel - American journal of respiratory cell and molecular biology (2021)
2. Genetic and biological hallmarks of colorectal cancer. - Jiexi Li;Xingdi Ma;Deepavali Chakravarti;Shabnam Shalapour;Ronald A DePinho - Genes & development (2021)
3. Tumor Microenvironment-Derived Metabolites: A Guide to Find New Metabolic Therapeutic Targets and Biomarkers. - Juan C García-Cañaveras;Agustín Lahoz - Cancers (2021)
4. Cancer metabolism: looking forward. - Inmaculada Martínez-Reyes;Navdeep S Chandel - Nature reviews. Cancer (2021)
5. Pyroptosis, metabolism, and tumor immune microenvironment. - Tiantian Du;Jie Gao;Peilong Li;Yunshan Wang;Qiuchen Qi;Xiaoyan Liu;Juan Li;Chuanxin Wang;Lutao Du - Clinical and translational medicine (2021)
6. Reproducible Lipid Alterations in Patient-Derived Breast Cancer Xenograft FFPE Tissue Identified with MALDI MSI for Pre-Clinical and Clinical Application. - Vanna Denti;Maria K Andersen;Andrew Smith;Anna Mary Bofin;Anna Nordborg;Fulvio Magni;Siver Andreas Moestue;Marco Giampà - Metabolites (2021)
7. Tumor microenvironment-activated cancer cell membrane-liposome hybrid nanoparticle-mediated synergistic metabolic therapy and chemotherapy for non-small cell lung cancer. - Wei Zhang;Chunai Gong;Ziqiang Chen;Ming Li;Yuping Li;Jing Gao - Journal of nanobiotechnology (2021)
8. Avenues of research in dietary interventions to target tumor metabolism in osteosarcoma. - Taiana Campos Leite;Rebecca Jean Watters;Kurt Richard Weiss;Giuseppe Intini - Journal of translational medicine (2021)
9. MiR-489-3p Reduced Pancreatic Cancer Proliferation and Metastasis By Targeting PKM2 and LDHA Involving Glycolysis. - Dan Zhang;Zhiwei He;Yiyi Shen;Jie Wang;Tao Liu;Jianxin Jiang - Frontiers in oncology (2021)
10. Aberrant lipid metabolism in cancer cells and tumor microenvironment: the player rather than bystander in cancer progression and metastasis. - Xiujing Yu;Shuyi Mi;Jun Ye;Guochun Lou - Journal of Cancer (2021)

... (164 more literatures)

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