Targeting Metabolism for Cancer Therapy

Abstract

Metabolic reprogramming contributes to tumor development and introduces metabolic liabilities that can be exploited to treat cancer. Chemotherapies targeting metabolism have been effective cancer treatments for decades, and the success of these therapies demonstrates that a therapeutic window exists to target malignant metabolism. New insights into the differential metabolic dependencies of tumors have provided novel therapeutic strategies to exploit altered metabolism, some of which are being evaluated in pre-clinical models or clinical trials. Here, we review our current understanding of cancer metabolism and discuss how this might guide treatments targeting the metabolic requirements of tumor cells.

Oxidative phosphorylation as a potential therapeutic target for cancer therapy

“…For their anabolic metabolism, cancer cells take up large amounts of nutrients such as glucose, glutamine and other amino acids, as well as fatty acids, in distinct proportions, depending on the tumor type . It has been thought for long that cancer cells would retrieve their bioenergetic needs mostly from glucose or alternatively from glutamine.…”

“…For their anabolic metabolism, cancer cells take up large amounts of nutrients such as glucose, glutamine and other amino acids, as well as fatty acids, in distinct proportions, depending on the tumor type. [1][2][3][4][5] It has been thought for long that cancer cells would retrieve their bioenergetic needs mostly from glucose or alternatively from glutamine. However, over the past few years, it has become clear that oxidative phosphorylation (OXPHOS), that is, mitochondrial ATP generation coupled to oxygen consumption, helps cancers to progress in vivo.…”

Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional

“…Tumour cells reprogram their energy metabolism to promote cell proliferation and tumour growth, and this ability is intimately linked to hypoxia, mitochondrial physiology, oxidative stress (OS) and autophagy, which can affect and be affected by response to chemotherapy, immunotherapy, and RT . There is abundant interest in developing novel cancer therapies that exploit these aberrant metabolic traits . Although drugs that target glycolytic enzymes, such as hexokinase, pyruvate kinase isozyme M2, and lactate dehydrogenase have been evaluated in preclinical studies, clinical success has been limited, and drugs targeting glycolysis have not yet been approved as anticancer agents .…”

Targeted therapy of esophageal squamous cell carcinoma: the NRF2 signaling pathway as target

“…It will be essential to focus on the esophagus to develop therapeutic strategies for NRF2 high ESCC. Additionally, in vivo studies will likely be more reliable than in vitro cell culture studies, as seen in recent cancer metabolism studies …”