Many articles focus on the new progress of cancer metabolism research!

Recommended meeting of editor: in the 2019 Development Forum of clinical mass spectrometry and high-end medical testing, editor compiled several research results to jointly interpret the new progress made by scientists in the field of cancer metabolism research and share with you! Photo source: www.pixabay.com [1] nature: the secret of "mutation" in the metabolic pathway of cancer cells doi: 10.1038/s41586-019-1678-1 recently, a new study led by researchers from the University of Chicago revealed why cancer cells consume and use nutrients differently than healthy cells, and how this difference promotes the survival and growth of cancer cells All cells need to generate energy to maintain life, but cancer cells need more energy for rapid growth and reproduction Understanding how different types of cells self sustain or metabolize is an attractive area of research because this process can be interrupted and exploited by the development of new drugs In addition, metabolism also plays a role in the reactivity of immune cells For decades, biologists have been working on the complexity of how cell metabolism affects its function The new study, published in nature, shows that lactate, an end product of metabolism, alters the function of macrophages and thus their behavior Lactic acid is the final product of Warburg effect and has long been considered as metabolic waste Recent studies have shown that lactate can regulate the function of many cell types (immune cells and stem cells) Therefore, lactate is not only a waste, but also a key regulator of cell function In recent years, although some progress has been made, the mechanism of lactate regulating cell function is still unknown Moreover, since Warburg effect is actually present in all types of cancer, it is possible to elucidate its mechanism for the development of a wide range of targeted therapies that may target multiple types of cancer 【2】 Nat commun: immunosuppressant resistance and metabolic imbalance doi: 10.1038/s41467-019-12361-9 Dana Farber Cancer Institute and Broad Institute of MIT Scientists at MIT and Harvard University reported that metabolic imbalances in some cancer patients after treatment with nivolumab, a checkpoint inhibitor, were related to drug resistance and shorter survival times of immunotherapy drugs The researchers said the chemical changes reflected the "adaptive resistance mechanism" of cancer cells or immune system after being treated with the anti-PD-1 antibody drug nivolumab, which was related to the reduced survival rate of patients with advanced melanoma and renal cancer The greater the change in amino acid tryptophan into a metabolite called canine urinary ammonia, the greater the impact on survival Checkpoint blockers like nivolumab are drugs that release molecular brakes on immune responses that cancer often uses to evade the attack of immune T cells One such molecular brake is called PD-1 In some patients and some cancer types, these drugs have been proved to be very effective in releasing T cells to attack tumors, but in general, these drugs can only help a small number of patients "One of the most important questions in oncology is who is responding to modern PD-1 inhibitors and who is not," said choueiri, director of the Dana Farber urogenital tumor lank center "[3] cell Rep: metabolic reprogramming of branched chain amino acids or promoting drug tolerance in lung cancer doi: 10.1016/j.celrep.2019.06.026 In recent years, although molecular targeted therapy has achieved remarkable success in the treatment of diseases, the rapid increase of drug tolerance has become the main obstacle for scientists to develop effective therapy for lung cancer So how does lung cancer cell adapt to targeted therapy? What is the molecular mechanism behind this adaptive behavior? Can this adaptive response be remembered by cancer cells? Answering these questions may help researchers understand the evolutionary mechanism of drug tolerance of cancer cells in molecular targeted therapy Recently, in a research report published in the international journal Cell reports, scientists from the Institute of Biochemistry and cell biology, Chinese Academy of Sciences and other institutions revealed the key role of metabolic reprogramming mediated by epigenetic regulation in promoting molecular targeted therapy of lung cancer resistance The researchers found that low-dose targeted drug pretreatment can promote EGFR mutant lung cancer cells to adapt to the subsequent high-dose drug therapy, thus showing a short-term drug tolerance state, and the sustained stimulation of low-dose drugs will strengthen the adaptive response, and ultimately promote the occurrence of drug tolerance of cancer cells 【4】 Dev cell: to reveal the regulatory pathway of macrocytosis in pancreatic cancer, which is helpful to target the metabolism of cancer cells, and to prevent the growth of cancer cells doi: 10.1016/j.devcel.2019.05.043 because of the urgent need for nutrients, the fast-growing pancreatic tumor seeks "fuel" through another way macrocytosis Scientists hope to stop the process, often called "cell drinking," which could lead to cancer starving drugs First, however, is basic information -- invisible molecular signals that drive the process Now, scientists from Sanford Burnham prebes Institute of medicine have identified a signaling pathway regulating macropinocytosis, which triggers tumor growth and key metabolic differences, and reveals new directions for drug development and patient treatment The results were published in the Journal of developmental cell To find the fatal weakness of pancreatic cancer metabolism, researchers say, we need to have a deeper understanding of how these tumors obtain nutrition Our research shows that, like human beings, pancreatic cancer metabolism is diverse Some pancreatic tumors can "up" or "down" macrocytosis, depending on the availability of glutamine Glutamine is an amino acid that plays a key role in the metabolism of rapidly growing cells Other tumors naturally have high levels of macrocytosis We also identified molecular regulatory factors for this process, which may eventually lead to individualized treatment "[5] NAT Med: methionine is the metabolic dependence of tumor initiating cells doi: 10.1038/s41591-019-0423-5 understanding cell metabolism has great potential to develop new therapies for cancer metabolic pathways Compared with normal tissue, the metabolic pathway of massive tumor cells has changed However, cancer cells in tumor are heterogeneous, and tumor initiating cells (TICs) are important therapeutic targets, but their metabolic characteristics are not clear In order to understand their metabolic changes, researchers from the Genome Research Institute of the Singapore Bureau of science, technology and research, Nanyang University of technology and the National University of Singapore carried out metabonomics and metabolite tracking analysis on tics The results showed that tics had a high level of methionine cycle activity and methylation rate, which was driven by mat2a The researchers found that high methionine cycle activity led to the consumption of methionine far more than its regeneration, leading to exogenous methionine addiction Photo source: www.pixabay.com [6] NAT methods: using bioluminescence to observe the metabolism of cancer cells in real time doi: 10.1038/s41592-019-0421-z recently, scientists from EPFL invented a method to quantify the glucose metabolism of cancer in real time by bioluminescence The new light probe is not radioactive, so it can be used in organisms, such as mice carrying tumor cells The results were published in nature methods In this study, the author first took a mouse labeled with luciferase The tumor expressing luciferase is made by taking cancer samples from patients and labeling them with luciferase, an enzyme that produces bioluminescence These labeled cells grow in mice to understand the basic biology of cancer and the development of effective cancer treatment Next, mice were injected with the first compound, which is not easily broken down in the blood Twenty four hours later, a second compound was injected, which reacted with the first compound only under very specific conditions 【7】 Nature: it is revealed that nnmt is the main metabolic regulatory protein of cancer-related fibroblasts Doi: 10.1038/s41586-019-1173-8 high grade serous carcinoma (hgsc) is a tumor type mainly originated from fallopian tube or ovary and spread in the whole abdominal cavity Hgsc is the most common and lethal form of ovarian cancer When the disease has spread, most of the patients are in advanced stage at the time of diagnosis The five-year survival rate of the disease is about 50% In a new study, researchers from the University of Chicago and other research structures in the United States revealed that a new therapeutic target may potentially prevent the rapid spread and prognosis related to hgsc through systematic investigation of tumors and their surrounding tissues, especially the normal cells called fibroblasts in the surrounding tissues The relevant research results were published in the Nature journal Until then, scientists had focused on the tumor itself, the researchers said Everyone does But in view of the lack of progress in this approach and the fact that tumors are surrounded by different types of tumor supporting cells (stroma), we think it might be better to pay less attention to cancer and pay more attention to stroma, which is the supporting tissue surrounding cancer and making it grow 【8】 Nature: scientists have successfully revealed the metabolic addiction of cancer doi: 10.1038/s41586-019-1150-2 Cancerous tumors are often classified according to their tissue sources However, in recent years, the development of human genome sequencing and DNA sequencing technology has ushered in a new era of precision oncology, in which patients will receive customized therapy aiming at specific mutations in their body tumors for cancer treatment This new therapy often achieves some important success, but recently many cancer researchers began to suspect that the occurrence of cancer in patients may affect the performance of specific mutations, which may play an important role in determining the response of patients to targeted therapy Recently, in a research report published in the international journal Nature, scientists from the University of California and other institutions described a new type of rules through their research, which can help predict the key aspects of tissue origin affecting the genetic composition of tumors, or have potentially important therapeutic value In this paper, the researchers studied a class of molecules called nicotinamide adenine dinucleotide (NAD) Nad is a key cofactor needed by many cell responses, including energy metabolism, epigenetic regulation and DNA damage response The researchers clarified the way cells make NAD, which has an important impact on cancer treatment 【9】 Nat metal: 7 times longer! Amino acid metabolism or leukemia fatal weakness! Doi: 10.1038/s42255-019-0039-6 compared with healthy cells, tumor cells consume sugar faster, but they also need amino acids, which are the basic components of proteins and other biological macromolecules Researchers at the Winship Cancer Institute at Emory University have found a