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The Journal of Experimental Medicine Jan 2021Dysregulation in lipid metabolism is among the most prominent metabolic alterations in cancer. Cancer cells harness lipid metabolism to obtain energy, components for... (Review)
Review
Dysregulation in lipid metabolism is among the most prominent metabolic alterations in cancer. Cancer cells harness lipid metabolism to obtain energy, components for biological membranes, and signaling molecules needed for proliferation, survival, invasion, metastasis, and response to the tumor microenvironment impact and cancer therapy. Here, we summarize and discuss current knowledge about the advances made in understanding the regulation of lipid metabolism in cancer cells and introduce different approaches that have been clinically used to disrupt lipid metabolism in cancer therapy.
Topics: Animals; Cell Proliferation; Humans; Immunotherapy; Lipid Metabolism; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Tumor Microenvironment
PubMed: 33601415
DOI: 10.1084/jem.20201606 -
Immunity Jan 2020Cancer immunotherapy is a validated and critically important approach for treating patients with cancer. Given the vast research and clinical investigation efforts... (Review)
Review
Cancer immunotherapy is a validated and critically important approach for treating patients with cancer. Given the vast research and clinical investigation efforts dedicated to advancing both endogenous and synthetic immunotherapy approaches, there is a need to focus on crucial questions and define roadblocks to the basic understanding and clinical progress. Here, we define ten key challenges facing cancer immunotherapy, which range from lack of confidence in translating pre-clinical findings to identifying optimal combinations of immune-based therapies for any given patient. Addressing these challenges will require the combined efforts of basic researchers and clinicians, and the focusing of resources to accelerate understanding of the complex interactions between cancer and the immune system and the development of improved treatment options for patients with cancer.
Topics: Humans; Immunotherapy; Models, Biological; Neoplasms; Tumor Microenvironment
PubMed: 31940268
DOI: 10.1016/j.immuni.2019.12.011 -
Molecular Cancer Feb 2022Ferroptosis is an intracellular iron-dependent form of cell death that is distinct from apoptosis, necrosis, and autophagy. Extensive studies suggest that ferroptosis... (Review)
Review
Ferroptosis is an intracellular iron-dependent form of cell death that is distinct from apoptosis, necrosis, and autophagy. Extensive studies suggest that ferroptosis plays a pivotal role in tumor suppression, thus providing new opportunities for cancer therapy. The development of resistance to cancer therapy remains a major challenge. A number of preclinical and clinical studies have focused on overcoming drug resistance. Intriguingly, ferroptosis has been correlated with cancer therapy resistance, and inducing ferroptosis has been demonstrated to reverse drug resistance. Herein, we provide a detailed description of the mechanisms of ferroptosis and the therapeutic role of regulating ferroptosis in reversing the resistance of cancer to common therapies, such as chemotherapy, targeted therapy and immunotherapy. We discuss the prospect and challenge of regulating ferroptosis as a therapeutic strategy for reversing cancer therapy resistance and expect that our review could provide some references for further studies.
Topics: Apoptosis; Drug Resistance; Ferroptosis; Humans; Immunotherapy; Neoplasms
PubMed: 35151318
DOI: 10.1186/s12943-022-01530-y -
Science (New York, N.Y.) Apr 2020Metabolic reprogramming is a hallmark of malignancy. As our understanding of the complexity of tumor biology increases, so does our appreciation of the complexity of... (Review)
Review
Metabolic reprogramming is a hallmark of malignancy. As our understanding of the complexity of tumor biology increases, so does our appreciation of the complexity of tumor metabolism. Metabolic heterogeneity among human tumors poses a challenge to developing therapies that exploit metabolic vulnerabilities. Recent work also demonstrates that the metabolic properties and preferences of a tumor change during cancer progression. This produces distinct sets of vulnerabilities between primary tumors and metastatic cancer, even in the same patient or experimental model. We review emerging concepts about metabolic reprogramming in cancer, with particular attention on why metabolic properties evolve during cancer progression and how this information might be used to develop better therapeutic strategies.
Topics: Animals; Disease Progression; Humans; Mice; Molecular Targeted Therapy; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Precancerous Conditions
PubMed: 32273439
DOI: 10.1126/science.aaw5473 -
Cells Oct 2020Aberrant metabolism is a major hallmark of cancer. Abnormal cancer metabolism, such as aerobic glycolysis and increased anabolic pathways, has important roles in... (Review)
Review
Aberrant metabolism is a major hallmark of cancer. Abnormal cancer metabolism, such as aerobic glycolysis and increased anabolic pathways, has important roles in tumorigenesis, metastasis, drug resistance, and cancer stem cells. Well-known oncogenic signaling pathways, such as phosphoinositide 3-kinase (PI3K)/AKT, Myc, and Hippo pathway, mediate metabolic gene expression and increase metabolic enzyme activities. Vice versa, deregulated metabolic pathways contribute to defects in cellular signal transduction pathways, which in turn provide energy, building blocks, and redox potentials for unrestrained cancer cell proliferation. Studies and clinical trials are being performed that focus on the inhibition of metabolic enzymes by small molecules or dietary interventions (e.g., fasting, calorie restriction, and intermittent fasting). Similar to genetic heterogeneity, the metabolic phenotypes of cancers are highly heterogeneous. This heterogeneity results from diverse cues in the tumor microenvironment and genetic mutations. Hence, overcoming metabolic plasticity is an important goal of modern cancer therapeutics. This review highlights recent findings on the metabolic phenotypes of cancer and elucidates the interactions between signal transduction pathways and metabolic pathways. We also provide novel rationales for designing the next-generation cancer metabolism drugs.
Topics: Carcinogenesis; Humans; Models, Biological; Molecular Targeted Therapy; Neoplasms; Phenotype; Signal Transduction
PubMed: 33081387
DOI: 10.3390/cells9102308 -
Cancer Science May 2020Artificial intelligence (AI) has contributed substantially to the resolution of a variety of biomedical problems, including cancer, over the past decade. Deep learning,... (Review)
Review
Artificial intelligence (AI) has contributed substantially to the resolution of a variety of biomedical problems, including cancer, over the past decade. Deep learning, a subfield of AI that is highly flexible and supports automatic feature extraction, is increasingly being applied in various areas of both basic and clinical cancer research. In this review, we describe numerous recent examples of the application of AI in oncology, including cases in which deep learning has efficiently solved problems that were previously thought to be unsolvable, and we address obstacles that must be overcome before such application can become more widespread. We also highlight resources and datasets that can help harness the power of AI for cancer research. The development of innovative approaches to and applications of AI will yield important insights in oncology in the coming decade.
Topics: Artificial Intelligence; Deep Learning; Genomics; Humans; Image Processing, Computer-Assisted; Medical Oncology; Neoplasms; Precision Medicine
PubMed: 32133724
DOI: 10.1111/cas.14377 -
Cancer Treatment Reviews Jun 2020In recent years, biotechnological breakthroughs have led to identification of complex and unique biologic features associated with carcinogenesis. Tumor and cell-free... (Review)
Review
In recent years, biotechnological breakthroughs have led to identification of complex and unique biologic features associated with carcinogenesis. Tumor and cell-free DNA profiling, immune markers, and proteomic and RNA analyses are used to identify these characteristics for optimization of anticancer therapy in individual patients. Consequently, clinical trials have evolved, shifting from tumor type-centered to gene-directed, histology-agnostic, with innovative adaptive design tailored to biomarker profiling with the goal to improve treatment outcomes. A plethora of precision medicine trials have been conducted. The majority of these trials demonstrated that matched therapy is associated with superior outcomes compared to non-matched therapy across tumor types and in specific cancers. To improve the implementation of precision medicine, this approach should be used early in the course of the disease, and patients should have complete tumor profiling and access to effective matched therapy. To overcome the complexity of tumor biology, clinical trials with combinations of gene-targeted therapy with immune-targeted approaches (e.g., checkpoint blockade, personalized vaccines and/or chimeric antigen receptor T-cells), hormonal therapy, chemotherapy and/or novel agents should be considered. These studies should target dynamic changes in tumor biologic abnormalities, eliminating minimal residual disease, and eradicating significant subclones that confer resistance to treatment. Mining and expansion of real-world data, facilitated by the use of advanced computer data processing capabilities, may contribute to validation of information to predict new applications for medicines. In this review, we summarize the clinical trials and discuss challenges and opportunities to accelerate the implementation of precision oncology.
Topics: Biomarkers, Tumor; Genomics; Humans; Neoplasms; Precision Medicine; Randomized Controlled Trials as Topic
PubMed: 32251926
DOI: 10.1016/j.ctrv.2020.102019 -
Signal Transduction and Targeted Therapy Jun 2020Ferroptosis is a new form of programmed cell death characterized by the accumulation of iron-dependent lethal lipid peroxides. Recent discoveries have focused on... (Review)
Review
Ferroptosis is a new form of programmed cell death characterized by the accumulation of iron-dependent lethal lipid peroxides. Recent discoveries have focused on alterations that occur in lipid metabolism during ferroptosis and have provided intriguing insights into the interplay between ferroptosis and lipid metabolism in cancer. Their interaction regulates the initiation, development, metastasis, therapy resistance of cancer, as well as the tumor immunity, which offers several potential strategies for cancer treatment. This review is a brief overview of the features characterizing the interaction between ferroptosis and lipid metabolism, and highlights the significance of this interaction in cancer.
Topics: Animals; Ferroptosis; Humans; Lipid Metabolism; Neoplasm Metastasis; Neoplasms
PubMed: 32606298
DOI: 10.1038/s41392-020-00216-5 -
Cancer Discovery Jul 2019During cancer progression, tumor cells undergo molecular and phenotypic changes collectively referred to as cellular plasticity. Such changes result from... (Review)
Review
During cancer progression, tumor cells undergo molecular and phenotypic changes collectively referred to as cellular plasticity. Such changes result from microenvironmental cues, stochastic genetic and epigenetic alterations, and/or treatment-imposed selective pressures, thereby contributing to tumor heterogeneity and therapy resistance. Epithelial-mesenchymal plasticity is the best-known case of tumor cell plasticity, but recent work has uncovered other examples, often with functional consequences. In this review, we explore the nature and role(s) of these diverse cellular plasticity programs in premalignant progression, tumor evolution, and adaptation to therapy and consider ways in which targeting plasticity could lead to novel anticancer treatments. SIGNIFICANCE: Changes in cell identity, or cellular plasticity, are common at different stages of tumor progression, and it has become clear that cellular plasticity can be a potent mediator of tumor progression and chemoresistance. Understanding the mechanisms underlying the various forms of cell plasticity may deliver new strategies for targeting the most lethal aspects of cancer: metastasis and resistance to therapy.
Topics: Animals; Cell Plasticity; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Humans; Metaplasia; Neoplasms; Neoplastic Stem Cells; Signal Transduction
PubMed: 30992279
DOI: 10.1158/2159-8290.CD-19-0015 -
Developmental Cell May 2021Tumors undergo metabolic transformations to sustain uncontrolled proliferation, avoid cell death, and seed in secondary organs. An increased focus on cancer lipid... (Review)
Review
Tumors undergo metabolic transformations to sustain uncontrolled proliferation, avoid cell death, and seed in secondary organs. An increased focus on cancer lipid metabolism has unveiled a number of mechanisms that promote tumor growth and survival, many of which are independent of classical cellular bioenergetics. These mechanisms include modulation of ferroptotic-mediated cell death, support during tumor metastasis, and interactions with the cells of the tumor microenvironment. As such, targeting lipid metabolism for anti-cancer therapies is attractive, with recent work on small-molecule inhibitors identifying compounds to target lipid metabolism. Here, we discuss these topics and identify open questions.
Topics: Animals; Diet; Ferroptosis; Humans; Lipid Metabolism; Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 33945792
DOI: 10.1016/j.devcel.2021.04.013