Cure Alveolar Soft Part Sarcoma International (iCureASPS)

The relevance of tyrosine kinase inhibitors for global metabolic pathways in cancer


Abstract

Tumor metabolism is a thrilling discipline that focuses on mechanisms used by cancer cells to earn crucial building blocks and energy to preserve growth and overcome resistance to various treatment modalities. At the same time, therapies directed specifically against aberrant signalling pathways driven by protein tyrosine kinases (TKs) involved in proliferation, metastasis and growth count for several years to promising anti-cancer approaches. In this respect, small molecule inhibitors are the most widely used clinically relevant means for targeted therapy, with a rising number of approvals for TKs inhibitors. In this review, we discuss recent observations related to TKs-associated metabolism and to metabolic feedback that is initialized as cellular response to particular TK-targeted therapies. These observations provide collective evidence that therapeutic responses are primarily linked to such pathways as regulation of lipid and amino acid metabolism, TCA cycle and glycolysis, advocating therefore the development of further effective targeted therapies against a broader spectrum of TKs to treat patients whose tumors display deregulated signalling driven by these proteins.

Keywords: Tyrosine kinase inhibitors, Metabolomics, Targeted therapies, Glycolysis, Glucose, TCA cycle, Energy metabolism, Amino acids, Lipid metabolism

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817809/

Global Profiling Strategies for Mapping Dysregulated Metabolic Pathways in Cancer



Cancer cells possess fundamentally altered metabolism that provides a foundation to support tumorigenicity and malignancy. Our understanding of the biochemical underpinnings of cancer has benefited from the integrated utilization of large-scale profiling platforms (e.g., genomics, proteomics, and metabolomics), which, together, can provide a global assessment of how enzymes and their parent metabolic networks become altered in cancer to fuel tumor growth. This review presents several examples of how these integrated platforms have yielded fundamental insights into dysregulated metabolism in cancer. We will also discuss questions and challenges that must be addressed to more completely describe, and eventually control, the diverse metabolic pathways that support tumorigenesis.


https://www.sciencedirect.com/science/a ... 3112003737

Main Text
Introduction
Cancer cells have fundamentally altered cellular metabolism, which directly contributes to tumorigenicity and malignancy. Deciphering the full scope of dysregulated metabolism in cancer and its relevance to disease pathogenesis and potential therapeutic relevance requires the advancement of technologies to identify altered enzymes and metabolites in cancer. This review will discuss how large-scale profiling methods, such as genomics, proteomics, and metabolomics, have been innovatively used to elucidate metabolic pathways that drive tumorigenesis and metastasis. Not only have such large-scale endeavors been useful in providing fundamental insights into the basic biochemistry that defines cancer cells, but they have also led to the discovery of potential targets for cancer therapy. We will also discuss challenges facing the field of cancer metabolism.