Cancer treatment and research最新文献

{"title":"Metabolic Reprogramming in Cancer Stem Cells.","authors":"Gaurav Ranjan, Srijani Dasgupta, Uttam Kumar Mishra, Priyashree Sunita, Shakti Prasad Pattanayak","doi":"10.1007/978-3-032-21861-2_8","DOIUrl":"10.1007/978-3-032-21861-2_8","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are a subset of tumor cells that exhibit self-renewal, differentiation potential, and resistance to conventional therapies. One of the characteristic traits of CSCs is their metabolic flexibility, with the ability to adapt energy production and biosynthesis in the context of low oxygen, limited nutrients, and therapy-driven stress. This adaptability allows them to survive, advances tumor development, and results in relapse after treatment.CSCs can switch between glycolysis and oxidative phosphorylation (OXPHOS) dynamically in different biological contexts. CSCs mainly produce ATP and synthesize nucleotides, amino acids, and lipids through glycolysis in hypoxia. OXPHOS is important for the maintenance of quiescent cells, for reducing reactive oxygen species (ROS) production, and supports long-term survival and tumor initiation. In addition to glucose, CSCs utilize lipid and amino acid metabolism. Fatty acid oxidation provides energy during stress, while glutamine, serine, and glycine support biosynthesis, redox homeostasis, and epigenetic control, collectively enhancing survival and therapy resistance. CSCs also rely on lipid and amino acid metabolism, in addition to glucose. Fatty acid oxidation is a source of energy during stress, and glutamine-, serine-, and glycine-derived metabolic products contribute to promoting biosynthesis for redox homeostasis, epigenetic regulation, and survival/therapy resistance. The tumor microenvironment (TME) dictates CSCs' metabolism through cross talk with fibroblasts, immune cells, and components of the extracellular matrix. Metabolic interplay, e.g., reverse Warburg effect, allows CSC to consume stromal metabolites, facilitating the promotion of tumor and resistance to therapy. Targeting of CSC metabolism, via glycolytic and mitochondrial inhibitors, lipid metabolism originated blockers, or amino acids modulators can perturb the survival of CSCs and increase tumor sensitivity to classical therapies. In this aspect, the application of combinatorial therapy was able to provide additional benefit by addressing both proliferative and quiescent CSC.In conclusion, metabolic reprogramming underpins CSC survival, drives therapy resistance, and promotes tumor progression. Exploiting these metabolic adaptations provides a promising strategy for achieving long-lasting and effective cancer therapies.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"195 ","pages":"155-174"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Metabolism and Dynamics in Cancer Cells.","authors":"Pedram Fadavi, Farzad Taghizadeh-Hesary","doi":"10.1007/978-3-032-21861-2_6","DOIUrl":"10.1007/978-3-032-21861-2_6","url":null,"abstract":"<p><p>Cancer metabolism has long been interpreted through Otto Warburg's original observation that malignant cells favor aerobic glycolysis due to defective mitochondria. Although foundational, this view is now recognized as incomplete. Contemporary evidence demonstrates that mitochondria in cancer cells remain highly functional and play indispensable roles far beyond adenosine triphosphate (ATP) production. Many tumors actively engage mitochondrial oxidative phosphorylation (OXPHOS) alongside glycolysis, enabling metabolic flexibility across the heterogeneous tumor microenvironment (TME). Mitochondria also generate reactive oxygen species (ROS) that stabilize hypoxia-inducible factor-1 (HIF-1), reinforcing pathways that promote angiogenesis, invasion, and survival under hypoxic stress. Beyond bioenergetics and redox regulation, mitochondria critically shape cancer progression through calcium homeostasis and dynamic remodeling. Meanwhile, mitochondrial fusion and fission govern organelle quality control and functional redistribution. Fusion sustains OXPHOS and cancer stem cell quiescence, whereas fission promotes proliferation, migration, immune evasion, and therapy resistance. Collectively, these findings establish mitochondria as central regulators of tumor evolution, influencing survival in the TME, immune escape, malignant upgrading, and resistance to chemotherapy, radiotherapy, and immunotherapy. Understanding mitochondrial biology, therefore, provides essential insight into cancer progression and reveals promising therapeutic opportunities.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"195 ","pages":"109-120"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Warburg Effect and Aerobic Glycolysis in Tumors.","authors":"Bhupender Nehra, Sourabh Suthar, Rishabh Kasnia, Sunaina Demiwal, Mohini Mondal, Himanshu Sharma, Naheed Mojgani","doi":"10.1007/978-3-032-21861-2_2","DOIUrl":"10.1007/978-3-032-21861-2_2","url":null,"abstract":"<p><p>A basic metabolic characteristic of carcinogenesis, namely the Warburg effect, is defined by the preferred utilization of aerobic glycolysis for energy generation in cancer cells, even in the presence of oxygen. Here, rapid proliferation and carefully planned adaptation to fulfill biosynthetic, redox, and survival requirements of malignant transformation are byproducts due to this adjustment in energy metabolism. Aerobic glycolysis enables tumor cells to accumulate metabolic intermediates, i.e., essential for macromolecular synthesis, supports redox homeostasis through NADPH production, and modulates tumor microenvironment via acidifying extracellular pH. Thereby, it leads to the promotion of invasion and immune evasion. Further, the discovery of this phenomenon by Otto Warburg nearly a century ago laid the foundation for modern cancer metabolism research. Advances in molecular oncology have since elucidated the regulatory role of oncogenes (such as MYC, RAS, and PI3K), tumor suppressors (like p53 and LKB1), and transcriptional networks (e.g., HIF-1α) to enforce glycolytic dependency. Recent studies further highlight that the Warburg effect integrates with mitochondrial signaling, epigenetic modifications, and metabolic cross talk between cancer cells as well as stromal components to provide novel therapeutic opportunities. This book chapter explores biochemical, molecular, and physiological dimensions of the Warburg effect along with its mechanistic basis, role in tumor progression, and emerging strategies to exploit glycolytic addiction in cancer therapy.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"195 ","pages":"21-43"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Metabolism in Cancer Therapy: Inhibitors and Approaches.","authors":"Bhabani Shankar Nayak, Bangmayee Dash, Sisir Nandi, Nebojša Pavlović, Mohamed Dkhi","doi":"10.1007/978-3-032-21861-2_9","DOIUrl":"10.1007/978-3-032-21861-2_9","url":null,"abstract":"<p><p>Cancer cells show different abnormal metabolic pathways that promote their development and viability. A novel therapeutic strategy has emerged for the treatment of cancer by inhibiting major metabolic pathways, such as the glycolysis pathway, pentose phosphate pathway (PPP), fatty acid synthesis, glutaminase inhibitors, and metabolism associated with mitochondrial pathways. Metabolic reprogramming supports the formation of tumors and metabolic liabilities, which are used to treat various cancers. Metabolic research on cancer metabolism was based on Otto Warburg's research work, which is related to aerobic glycolysis. In combination with chemotherapies, the reprogramming of cancer metabolism has been efficacious in treating neoplastic cells. The success of the novel treatment demonstrates an emerging therapeutic approach towards cancer and its management, some of which are being examined in preclinical models. A number of metabolic molecules have been used to target the progression of preclinical observation, which are associated with nucleic acid synthesis and other major biochemical processes. With the advancement of multi-omics, single-cell, and other spatial technologies, we can easily track metabolism more accurately.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"195 ","pages":"175-191"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction to Cancer Metabolism.","authors":"Gomathi Mohan, Mukesh Meena, Manzer H Siddiqui, Gaurav Raturi, Pracheta Janmeda, Priya Chaudhary","doi":"10.1007/978-3-032-21861-2_1","DOIUrl":"10.1007/978-3-032-21861-2_1","url":null,"abstract":"<p><p>The fact that tumor cells have a distinct metabolic phenotype from their normal equivalents is becoming more widely recognized. Tumor metabolism exhibits a complex ecological network due to the presence of multiple metabolic compartments interconnected through the transfer of catabolites. Tumor cells exhibit markedly elevated rates of metabolism for fatty acids, glutamine, acetate, hydroxybutyrate, pyruvate, lactate, and glucose compared to nontumor cells. Tumor cells can generate adenosine triphosphate (ATP) as the fundamental energy unit due to their metabolic flexibility and unpredictability, which aids in maintaining the redox balance and distributing resources to essential biosynthetic activities necessary for cell proliferation, growth, and survival. Experimental data indicate that cancer growth may be induced by metabolic cross talk between cell populations exhibiting distinct, synergistic metabolic characteristics. Thus, emphasizing the metabolic variations between tumor and normal cells presents a suitable approach for anticancer strategies. Cancer cells adapt their metabolism and influence the metabolic processes of surrounding cells within the microenvironment of the tumor to ensure their proliferation and survival. This process drives disease progression; specifically, we identify targetable metabolic weaknesses that can be intervened upon.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"195 ","pages":"1-20"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers of Cancer Metabolism and Therapeutic Response.","authors":"Hamid Tanzadehpanah, Ali Ahmadizad Firouzjaei, Nafiseh Izadi, Mona Mansourian, Amir Hossein Esfandiari, Khatere Mokhtari, Fatemeh Forouzanfar, Hamed Afkhami, Mahdieh Ameri Shah Reza, Mohsen Sheykhhasan, Hanie Mahaki","doi":"10.1007/978-3-032-21861-2_10","DOIUrl":"10.1007/978-3-032-21861-2_10","url":null,"abstract":"<p><p>Insight into the metabolic reprogramming of cancer cells provides not only an understanding of the biology of the tumor but also novel biomarkers for diagnosis, prognosis, and therapy response monitoring. Cellular differentiation of tumors can be characterized by enhanced glycolysis, which is in accordance with changes in mitochondrial function and nutritional utilization. Elevated blood lactate and some amino acids have also been linked to tumor malignancy and unfavorable prognosis. Recent technologies, such as magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), have advanced the detection of metabolic biomarkers. These methodologies enable the comprehensive metabolic profiling of tumor tissues and body fluids, which can identify specific metabolites with the potential to be used as biomarkers. In addition, the combination of genomics and proteomics with metabolomics has offered enhanced insights into cancer metabolism and has revealed the potential for the discovery of new therapeutic targets. They have also recognized the possibility of employing noninvasive imaging methods, such as positron emission tomography using radioactively labeled metabolites, to image tumor metabolism in real time. Such imaging modalities have the potential for delivering dynamic images of metabolic events occurring during treatment and offer a potent tool for monitoring treatment response and adapting the treatment plan accordingly.This book chapter discusses the status of cancer metabolic biomarkers and their discovery from the laboratory to clinical application potential.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"195 ","pages":"193-220"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer and Immune Cells: A Metabolic Battle in the Tumor Microenvironment.","authors":"Sam Pournezhad, Ramyar Azar, Farzad Taghizadeh-Hesary","doi":"10.1007/978-3-032-21861-2_11","DOIUrl":"10.1007/978-3-032-21861-2_11","url":null,"abstract":"<p><p>Immunometabolism has emerged as a critical field that links cellular energy regulation with immune function, including in the context of cancer. The tumor microenvironment (TME) is characterized by hypoxia, acidosis, and nutrient competition, all of which promote metabolic reprogramming in cancer cells while suppressing immune surveillance. Antitumor immune cells such as cytotoxic T lymphocytes, natural killer (NK) cells, and M1 macrophages rely on glycolysis and oxidative phosphorylation to sustain effector functions. In contrast, tumor-promoting cells, including regulatory T cells, myeloid-derived suppressor cells, and M2 macrophages, adopt oxidative metabolism and immunosuppressive pathways that reinforce immune escape. Cancer cells further evade immunity through immune checkpoint expression, reduced antigen presentation, secretion of suppressive cytokines, and mitochondrial hijacking, gaining bioenergetic superiority over immune cells. Current immunotherapies, such as checkpoint inhibitors, CAR-T cell therapy, cancer vaccines, and NK-cell-based therapies, have transformed cancer treatment but are often limited by TME-induced metabolic suppression. This chapter highlights the central role of metabolism in cancer-immune dynamics and introduces a novel therapeutic framework that integrates metabolic intervention with immune activation for improved cancer treatment outcomes.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"195 ","pages":"221-235"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamine Metabolism: Role in Cancer Cell Proliferation and Survival.","authors":"Aganta Chakraborty, Sanket Pramanik, Shrabasti Mullick, Rajarshi Nath, Mohini Mondal, Radheshyam Pal, Sumel Ashique, Mayukh Jana","doi":"10.1007/978-3-032-21861-2_3","DOIUrl":"10.1007/978-3-032-21861-2_3","url":null,"abstract":"<p><p>Glutamine is crucial for cancer cell proliferation and survival because it fuels the TCA cycle, provides building blocks for macromolecules, and helps maintain redox balance by supporting antioxidant pathways like glutathione production. Cancer cells often become dependent on glutamine, a phenomenon known as glutaminolysis, and use it to produce energy and essential molecules for rapid growth. This metabolic addiction makes glutamine metabolism a significant target for cancer therapies. In recent years, some therapeutic drugs targeting glutamine metabolism to treat cancer have been developed. However, such drugs are not sufficiently effective. Targeting metabolic reprogramming may be an effective strategy to enhance cancer treatment efficacy. Glutamine serves as a vital nutrient for cancer cells. Inhibiting glutamine metabolism has shown promise in preventing tumor growth both in vivo and in vitro through various mechanisms.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"195 ","pages":"45-78"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tools and Technologies for Studying Cancer Metabolism.","authors":"Ayush Madan, Subhajit Mandal, Soukat Chandra, Joy Das, Biplab Debnath","doi":"10.1007/978-3-032-21861-2_12","DOIUrl":"10.1007/978-3-032-21861-2_12","url":null,"abstract":"<p><p>Tools for studying cancer metabolism include mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy for metabolomics, metabolic imaging (PET, MRI, MRS) for in vivo analysis, and metabolic flux analysis (MFA) with stable isotope tracers to track metabolic pathways. Other technologies involve microfluidic systems for simulating tumor environments and fluorescence-activated cell sorting (FACS)-based methods for analyzing immune cell metabolism. Multiple analytical platforms that facilitate the detection of metabolites in cells and living organisms have been utilized to study cancer metabolism. In this section, we will discuss how these techniques have contributed to the study of cancer metabolism and how they have led to advances in our understanding of metabolic reprogramming and biological phenotypes.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"195 ","pages":"237-247"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Oxidative Stress and Redox Regulation in Cancer.","authors":"Nahid Nafissi, Pedram Fadavi, Farzad Taghizadeh-Hesary","doi":"10.1007/978-3-032-21861-2_5","DOIUrl":"10.1007/978-3-032-21861-2_5","url":null,"abstract":"<p><p>Oxidative stress is a pivotal regulator of cancer biology, influencing both the initiation and progression of malignancy. Oxidative stress results from an imbalance between the generation of reactive oxygen species (ROS) and the ability of antioxidant systems to detoxify them. While physiological levels of ROS are essential for cellular homeostasis, excessive ROS can damage DNA, proteins, and lipids, leading to cellular death. Paradoxically, cancer cells rely on moderately elevated ROS levels to sustain proliferative signaling, metabolic reprogramming, and invasion. To prevent oxidative damage, they rewire their redox networks by simultaneously increasing ROS production and enhancing antioxidant defense lines. Meanwhile, cancer stem cells (CSCs) keep even tighter redox control by preserving intrinsically low ROS levels through metabolic adaptation and robust antioxidant capacity. Elevated ROS not only promotes tumor growth but also modulates the tumor microenvironment (TME), inducing immune evasion, epithelial-mesenchymal transition, and therapy resistance. Clinically, targeting redox balance has become a promising approach for cancer diagnosis and treatment. This Chapter is dedicated to provide a practical summary of current knowledge on oxidative stress in cancer cells and how it contributes to cancer formation and progression.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"195 ","pages":"95-107"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}