Metabolomics in Oncology

Introduction:

Metabolic reprogramming has been seen as a hallmark of cancer progression. Metabolomic analysis of many metabolic profiles represents a robust and technically feasible method to evaluate dynamic changes in tumor metabolism and response to treatment over the progression of the disease. Various studies have highlighted the use of metabolomics in different aspects of tumor metabolic reprogramming research to date.

Metabolomics techniques can help understand the effects of change in the metabolic profile of the tumor microenvironment on the three major metabolic pathways of tumors. Many non-invasive biofluids are available that produce accurate and valuable clinical information on tumor metabolism to find out early biomarkers of tumor development. Likewise, metabolomics can predict individual metabolic differences in response to tumor drugs, examine drug efficacy, and monitor drug resistance.

What Are Metabolomics?

Metabolomics is the evaluation of small molecules, generally called metabolites, within cells, biofluids, tissues, or organisms on a huge scale. Combined, these small molecules and their relation to the biological system are known as the metabolome.

Like genomics, which is the evaluation of the DNA (deoxyribonucleic acid) and genetic information within a cell, and transcriptomics is the study of RNA (ribonucleic acid) and differences in mRNA, metabolomics is the study of substrates and products of metabolism, which are influenced by genetic and environmental factors.

Metabolomics is a robust approach since metabolites and their concentration reflect the underlying biochemical process and type of cells or tissues. Therefore, metabolomics represents the molecular phenotype in the best possible way.

What Is the Role Of Metabolomics in Oncology (Cancer)?

While cancer development, metabolic reprogramming gives cancer cells the potential to survive and proliferate. The most known is the Warburg effect, which suggests that the aerobic glycolysis pathway is very much related to the occurrence of cancer. In addition, deregulated anabolism or catabolism of fatty acids (FAs) and amino acids, especially glutamine, serine, and glycine, have been shown to work as a metabolic regulator in helping cancer cell growth. The occurrence and development of cancer cells are closely associated with the three metabolic pathways, the regulation of the three pathways of cancer cells, and the way they crossover. Metabolomics might be used to supplement tumor metabolism by evaluating the metabolic profiles of various tumors.

• Metabolomic Markers in Cancer Progression: With the development of modern molecular biology, various new tumor markers carry necessary clinical value for the early diagnosis and screening of malignant tumors. However, the current tumor markers do not have sensitivity and specificity for the early diagnosis of tumors. As an emerging omics technology, metabolomics mostly involves the study of small molecular metabolites. It reflects a sequence of small changes in the body at the level of metabolites, which is appropriate for identifying diseases. Many researchers have used various detection techniques to research the early diagnosis and treatment prediction of tumors. Metabolomics methods are used to identify and validate metabolic biomarkers that correctly and sensitively identify tumor field progression and metastasis in a clinical setting. Furthermore, such efforts might be left to clinicians with accurate time frames to promote early and effective therapeutic interventions, significantly improving tumor patients' five-year survival rate.

• Application of Metabolomics for the Study of Tumor Drug Efficacy: The primary aim of drug therapy for tumors is to control the tumor's growth and improve patients' quality of life. Choosing the most effective anti-tumor drugs has become a main priority. In clinical practice, metabolomics can identify body or cell metabolites that reflect the effects of anti-tumor drugs on the body or cells to improve the efficacy of drugs and reduce avoidable adverse reactions. NMR (nuclear magnetic resonance) spectroscopy was used to identify metabolic alterations following adriamycin (ADR) treatment for gastric adenocarcinoma. After human gastric adenocarcinomas were implanted into mice, ADR was intraperitoneally injected for five days, and urine was collected on days two and five. Results showed that trimethylamine oxide, hippurate, and taurine levels were decreased in the tumor model and elevated following ADR treatment. Moreover, the levels of 2-oxoglutarate, 3-indoxyl sulfate, trigonelline, and citrate, which were all raised in the tumor model, significantly decreased to those of normal controls following ADR treatment. A plasma metabolomics study of 54 patients with colorectal cancer who received capecitabine before and after treatment revealed that the content of low-density lipoprotein-derived lipids was positively associated with drug toxicity during treatment.

• Application of Metabolomics in the Evaluation of Drug Resistance in Cancer: The metabolic sequence of tumor cells changes following the development of drug resistance. The same drug can develop various metabolic changes in sensitive and drug-resistant cells. Thus, metabolomics can determine metabolic changes in cells and their response to drugs to determine whether the tumor cells are resistant to drugs and evaluate drug resistance as soon as possible. As a fast, simple, and effective method, metabolomics uses a multivariable and dynamic way to determine metabolic results across a range of physiological and pathological states, which allows the prediction and assessment of patients' sensitivity and drug resistance to chemotherapy.

Metabolomics helps distinguish between platinum resistance and metabolite levels. LC-MS (Liquid chromatography- Mass Spectrometry) is used to characterize the levels of steroids, active estrogen, and sulfated or aldehyde glucose in the growth of platinum resistance in ovarian cancer. It was noted that these metabolites are primarily expressed in carboplatin-sensitive cells.

In a research conducted on non-small cell lung cancer (NSCLC), cisplatin-resistant cells were considered more sensitive to nutrient deprivation than those of sensitive cells, and adding glutamine to cisplatin-resistant cells restored cell death due to nutrient deprivation by elevating the intracellular nucleotide.

What Are the Biomarkers in Oncology (Cancer)?

There are four main classes of biomarkers in oncology:

• Molecular Biomarker: These are the molecules that help in the diagnosis and prognosis of the cancer, such as serum, fluid, biopsy, or plasma.

• Histologic Biomarker: These include tissue samples that are investigated under the microscope. It is a gold standard for diagnosing cancer, but these biomarkers are time-consuming, invasive, and expensive.

• Physiologic Biomarkers: These include physiological processes, such as blood flow and blood pressure.

• Radiographic Biomarker: These are the imaging biomarkers in oncology that can be identified in the images. These are the first steps in the diagnosis of cancer.

Conclusion:

Metabolomics is used across various aspects of cancer research, including cancer pathophysiology, biomarker discovery, and therapeutic response. The Metabolomics process can be used to evaluate the dynamics of tumor metabolism and response to treatment throughout the disease. Moreover, another aspect of increasing importance is the identification of biomarkers for personalized treatment strategies. At the same time, the metabolomic evaluation might also produce more accurate and precise clinical information about the metabolic needs of the tumor, as well as the determination of new pharmacodynamic biomarkers and the monitoring of drug resistance of the tumor.