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Cancer metabolism and metabolomics

Cancer is a major disease burden that affects both genders and causes considerable worldwide mortality and morbidity. Detection at an early stage and understanding the metabolism of cancer, both during progression and regression of the disease, is essential for better treatment outcomes. Also, an in‐depth understanding of the pathophysiology of cancer is essential in order to develop patient‐tailored therapy. The study of cancer metabolism, using various techniques and methods, is an important area of research. Regarding this, several studies have addressed the potential role of various MR methods in improving our understanding of the different aspects of tumor metabolism related to the progression and aggressiveness of malignancy, and the changes that occur during therapy. In recent years, the area of metabolomics has also found widespread use in the diagnosis of various disease processes, such as transcriptomics and proteomics. It measures small molecules (low molecular weight metabolites) within cells, tissues or whole organisms. Both qualitative and quantitative changes of metabolites in real time can be monitored using these approaches. These may arise due to alterations in metabolic pathways that occur because of genetic modification, physiological and/or pathophysiological stimuli. Of the various techniques used to study metabolomics, mass spectrometry and NMR have been widely employed to detect and quantify metabolites. Notably, MR methodologies are being continuously developed at a very rapid pace to understand cancer metabolism and to identify new biomarkers for early disease diagnosis and therapy monitoring. The journey to produce this special issue began in April 2017 at the editorial board meeting of NMR in Biomedicine at the International Society for Magnetic Resonance in Medicine (ISMRM) meeting in Honolulu, Hawaii. It was felt that an issue that highlights the role of different MR methodologies, both in human and animal models, in understanding the metabolism of cancer and the potential of metabolomics in cancers, would be timely. This issue consists of 16 articles (14 reviews and 2 original articles) written by leading experts. These contributions are arranged in such a way as to highlight the current knowledge, challenges, and future directions in these areas for wider dissemination. One of the hallmarks of cancer is the activated choline metabolism, characterized by increased levels of phosphocholine, glycerophosphocholine and total choline‐containing compounds. The alterations in the choline metabolism of cancer have been widely studied using magnetic resonance spectroscopy (MRS), and the majority of those studies have focused on phosphocholine and the Kennedy pathway. The importance of glycerophosphocholine in cancer metabolism has been realized, and the first review by Sonkar et al presents a summary of recent works examining the role of glycerophosphocholine in cancer and its detection by MRS. Another hallmark of cancer is lipid metabolism, which is altered during malignant transformation and during therapy. The assessment of lipids would thus be valuable. MRS and other molecular imaging methods have been used to study oncogenic transformations and examine the changes in lipids in response to a wide array of anticancer strategies, including chemotherapy, radiation therapy, signal transduction inhibitors, gene therapy and immunotherapy, or a combination of these strategies. Arlauckas et al review the role of lipid metabolism in cancer and its response to therapy, and also summarize the current field and areas of unmet needs. The measurement of neuronal and glial energy metabolism, and glutamate and GABA neurotransmitter cycling in the brain, by the use of C MRS and H‐C MRS in human and animal models, are reviewed by Rothman et al. The neuroenergetic and neurotransmitter cycling pathways studied by C MRS and the experimental validation of these measurements are presented. The review also summarizes the results of applications of C MRS in neurological and psychiatric diseases, diabetes, Alzheimer's disease, healthy aging and brain cancer. Limitations of the methods used and a summary of recent progress are also provided. Breast tumors being heterogeneous, their metabolism differs from other tumor subtypes, and also during disease progression. Studies have documented that the patient's outcome from therapy depends on several factors such as hormone receptor status, lymph node involvement and tumor grade. Furthermore, the response variation among patients following therapy may be related to how the cancer progresses and alters its metabolism. It is likely that such metabolic alterations are related to drug resistance observed in patients. Thus, the study of breast cancer metabolism is essential for early detection, diagnosis and response evaluation of tumors to interventions and therapies. Jagannathan, in his review, describes the role of various in vivo MR methodologies used in the study of breast cancer metabolism. Prostate cancer in men is extremely variable in its aggressiveness and progression. Low‐ or intermediate‐risk patients with localized cancer face a dilemma in selecting appropriate therapies. For example, whether to undergo aggressive treatments like surgery or whole‐gland radiation therapy with their associated complications, or undertake active surveillance without treatment. In this direction, focal therapies like high‐ intensity focused ultrasound (HIFU) have recently been the treatment of choice, thereby reducing the risk of complications of radical therapy.