Targeting Oncometabolites in Peritoneal Cancers: Preclinical Insights and Therapeutic Strategies

Abstract

Peritoneal cancers present significant clinical challenges with poor prognosis. Understanding the role of cancer cell metabolism and cancer-promoting metabolites in peritoneal cancers can provide new insights into the mechanisms that drive tumor progression and can identify novel therapeutic targets and biomarkers for early detection, prognosis, and treatment response. Cancer cells dynamically reprogram their metabolism to facilitate tumor growth and overcome metabolic stress, with cancer-promoting metabolites such as kynurenines, lactate, and sphingosine-1-phosphate promoting cell proliferation, angiogenesis, and immune evasion. Targeting cancer-promoting metabolites could also lead to the development of effective combinatorial and adjuvant therapies involving metabolic inhibitors for the treatment of peritoneal cancers. With the observed metabolomic heterogeneity in cancer patients, defining peritoneal cancer metabolome and cancer-promoting metabolites holds great promise for improving outcomes for patients with peritoneal tumors and advancing the field of precision cancer medicine. This review provides an overview of the metabolic signatures of peritoneal cancer cells, explores the role of cancer-promoting metabolites as potential therapeutic targets, and discusses the implications for advancing precision cancer medicine in peritoneal cancers.

Systems Biology in Cancer Diagnosis Integrating Omics Technologies and Artificial Intelligence to Support Physician Decision Making

“…Cancer is the leading cause of death in people, accounting for an estimated 10 million deaths by 2020 [4]. It is a complex disease resulting from anomalies in physiological processes involving genes, coding and non-coding RNAs, proteins, metabolites, and other biomolecules [5,6]. To understand such a complex disease from its onset to its progression, multi-omics analysis of these numerous bio-entities is required.…”

Editorial: Metabolome in gastrointestinal cancer

“…This points to the relevance of the metabolism in GI development and the importance of profiling the GI metabolome to understand the mechanisms underlying cancerogenesis and, even more, the progression ( 6 , 7 ). Metabolites are proven to play an increasingly versatile role in biological interactions, not only as substrates and products of enzyme-driven reactions but also as crucial system regulators ( 8 ). Cancer cells can repurpose these systems to drive unwanted proliferation, survival, and growth in cancer, and they can alter their metabolism during progression because of the dynamic interaction with the tumor microenvironment and the availability of metabolic factors such as glucose, amino acids and oxygen ( 9 ).…”