Case Report, Jrgm Vol: 12 Issue: 5
Metabolic reprogramming in tumor microenvironments: Targeting cancer's achilles' heel
Saman Pouyssegur*
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Dong’An Road, Shanghai, People’s Republic of China
*Corresponding Author: Saman Pouyssegur
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Dong’An Road, Shanghai, People’s Republic of China
E-mail: samanpouyssegur@yahoo.com
Received: 04-Sep-2023, Manuscript No. JRGM-23-116999;
Editor assigned: 05-Sep-2023, PreQC No. JRGM-23-116999 (PQ);
Reviewed: 19- Sep -2023, QC No. JRGM-23-116999;
Revised: 23-Sep -2023, Manuscript No. JRGM-23-116999 (R);
Published: 30- Sep-2023, DOI:10.4172/2325-9620.1000273
Citation: Pouyssegur S (2023) Metabolic Reprogramming In Tumor Microenvironments: Targeting Cancer’s Achilles’ Heel. J Regen Med 12:5.
Copyright: © 2023 Daniel M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Introduction
Cancer, a group of diseases characterized by uncontrolled cell growth, is a major global health concern. Despite significant advances in understanding and treating cancer, it remains a formidable challenge. One emerging area of research that offers promise in the battle against cancer is metabolic reprogramming in tumor microenvironments. This article explores how cancer cells undergo metabolic changes and how targeting these changes might represent a vulnerable point in cancer treatment [1].
Understanding metabolic reprogramming
To fuel their rapid growth and proliferation, cancer cells undergo a fundamental shift in how they produce and utilize energy. This metabolic reprogramming allows them to meet the high demands of a growing tumor. One of the most notable metabolic changes observed in cancer cells is the preference for aerobic glycolysis, a process that converts glucose into energy even in the presence of oxygen. This phenomenon, known as the Warburg effect, is less efficient in terms of energy production compared to oxidative phosphorylation. However, it allows cancer cells to generate energy rapidly and supports the synthesis of macromolecules required for their rapid proliferation. Cancer cells adapt to their environment by shifting their nutrient preferences. In addition to glucose, they rely on alternative energy sources like glutamine, fatty acids, and amino acids to sustain their growth. This adaptability makes them less dependent on a single nutrient source, enhancing their resilience. As a consequence of increased glycolysis, cancer cells produce lactate as a metabolic by-product. This lactate is often released into the tumor microenvironment, contributing to an acidic pH. This acidity supports tumor invasiveness and discourages immune responses. The tumor microenvironment plays a critical role in shaping metabolic reprogramming. It can be characterized by hypoxia, where tumor growth outpaces the supply of oxygen via blood vessels. In response to hypoxia, cancer cells upregulate hypoxia-inducible factor 1 (HIF-1), which promotes glycolysis and suppresses oxidative phosphorylation. The tumor microenvironment is not exclusively comprised of cancer cells; it includes various stromal cells, such as Cancer-Associated Fibroblasts (CAFs). These stromal cells can provide cancer cells with metabolites, including lactate and ketones, which help meet their energy and biosynthetic demands [2].
Metabolic vulnerabilities in cancer cells
The metabolic reprogramming that cancer cells undergo provides several potential vulnerabilities that can be exploited for therapeutic purposes:
Glucose dependency: The high glucose consumption of cancer cells presents a potential Achilles’ heel. Various strategies have been explored to target glucose metabolism, including the inhibition of glucose transporters and glycolytic enzymes [3].
Glutamine addiction: Some cancer cells become heavily reliant on glutamine, a non-essential amino acid that plays a crucial role in nucleotide and amino acid synthesis. Targeting glutamine metabolism, through the inhibition of enzymes like glutaminase, has shown promise in preclinical studies.
Mitochondrial dysfunction: Mitochondria are essential for oxidative phosphorylation, a process that cancer cells often suppress in favor of glycolysis. This offers opportunities to target the vulnerabilities associated with mitochondrial dysfunction, disrupting cancer cell metabolism.
Lactate transport: Inhibition of lactate transporters can lead to intracellular acidification, rendering cancer cells more vulnerable to other treatment strategies [4].
Targeting metabolic reprogramming in cancer therapy
To combat cancer by exploiting metabolic vulnerabilities, researchers are developing and testing a variety of therapeutic approaches:
Small molecules that target glycolytic enzymes, such as hexokinase and lactate dehydrogenase, have shown promise in preclinical studies. These inhibitors aim to disrupt glycolysis, depriving cancer cells of their primary energy source and hindering tumor growth. Drugs designed to inhibit glutaminase, an enzyme essential for glutamine metabolism, are being explored as a means to starve cancer cells of this critical nutrient. Compounds that specifically target dysfunctional mitochondria within cancer cells are being developed. They aim to disrupt the balance between glycolysis and oxidative phosphorylation, pushing cancer cells into an energy crisis. Metabolic reprogramming within tumor microenvironments can significantly affect immune cell function. Therefore, combining metabolic therapies with immune modulation, such as immune checkpoint inhibitors targeting PD-1 and CTLA-4, may enhance the body’s antitumor immune response [5].
Conclusion
Metabolic reprogramming in tumor microenvironments is a burgeoning field that holds great potential for revolutionizing cancer treatment. Understanding how cancer cells alter their metabolism to support their rapid growth has uncovered vulnerabilities that can be targeted for therapeutic benefit. By disrupting the metabolic reprogramming of cancer cells, we may find a path to more effective and tailored cancer treatments. As research in this field continues to advance, the future looks promising for better therapies that not only target cancer cells directly but also exploit their metabolic weaknesses. Combining metabolic therapies with established treatments such as chemotherapy, radiation therapy, and immunotherapy may provide a multi-pronged approach to combat this complex and challenging disease, improving the prognosis for cancer patients worldwide.
References
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- Tuerhong A, Xu J, Shi S, Tan Z, Meng Q, et al (2021) Overcoming chemoresistance by targeting reprogrammed metabolism: the Achilles' heel of pancreatic ductal adenocarcinoma. Cellular and Mol Life Sci, 78(14):5505-5526.
- Lebedev T, Kousar R, Patrick B, Usama M, Lee MK, et al (2023) Targeting ARID1A-Deficient Cancers: An Immune-Metabolic Perspective. Cells, 12(6):952.
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