The pathways that regulate fatty acid metabolism and homeostasis in cancer cells play distinctive pro-oncogenic roles under varying metabolic conditions and during various stages of tumor development. Initial work in this area was primarily focused on inhibitors targeting de novo fatty acid synthesis, with some compounds making it to clinical trials. However, the high degree of plasticity in cancer cells proved to be a major challenge, as cancer cells, upon inhibition of de novo synthesis, switched to extracellular uptake pathways for fatty acid acquisition. That led to the exploration of lipid uptake and other connected pathways as complementary therapeutic targets, which demonstrated beneficial effects in several clinical or preclinical models.
Targeting fatty acid synthesis was initially thought to be a promising antineoplastic therapy. However, despite two decades of intensive research and efforts, this approach was not completely translated into effective clinical outcomes. One of the primary reasons for that is the plasticity of the metabolic pathways. It was often observed that when one metabolic pathway was blocked, the cancer cells switched to an alternate pathway. In some cases, the ubiquitous nature of these pathways hindered the successful development of targeting drugs. Recent advances in this research area suggest that targeting the other interconnected pathways that regulate cancer cells' fatty acid metabolism and homeostasis demonstrates beneficial effects in several clinical or preclinical models. Recent research on implementing novel combinatorial strategies also provides a positive outlook. These new strategies mainly focus on exploiting a cancer cell's context and tissue-specific fatty acid requirements.
This research topic focuses on emerging antitumor therapeutic strategies targeting fatty acid metabolism. We welcome submissions focused on:
• Clinical or preclinical targeting of fatty acid synthesis, desaturation, uptake, activation, oxidation, or transport.
• Clinical or preclinical targeting of intracellular lipolysis, triglyceride synthesis, phospholipid modification, and upstream regulators of fatty acid metabolism
• Metabolic synthetic lethality, such as co-targeting multiple enzymes within fatty acid metabolism-related pathways to combat the plasticity of these pathways
• Devising strategies to make the fatty acid metabolism-related pathways less dispensable for cancer cell survival by modulating the tumor microenvironment.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
The pathways that regulate fatty acid metabolism and homeostasis in cancer cells play distinctive pro-oncogenic roles under varying metabolic conditions and during various stages of tumor development. Initial work in this area was primarily focused on inhibitors targeting de novo fatty acid synthesis, with some compounds making it to clinical trials. However, the high degree of plasticity in cancer cells proved to be a major challenge, as cancer cells, upon inhibition of de novo synthesis, switched to extracellular uptake pathways for fatty acid acquisition. That led to the exploration of lipid uptake and other connected pathways as complementary therapeutic targets, which demonstrated beneficial effects in several clinical or preclinical models.
Targeting fatty acid synthesis was initially thought to be a promising antineoplastic therapy. However, despite two decades of intensive research and efforts, this approach was not completely translated into effective clinical outcomes. One of the primary reasons for that is the plasticity of the metabolic pathways. It was often observed that when one metabolic pathway was blocked, the cancer cells switched to an alternate pathway. In some cases, the ubiquitous nature of these pathways hindered the successful development of targeting drugs. Recent advances in this research area suggest that targeting the other interconnected pathways that regulate cancer cells' fatty acid metabolism and homeostasis demonstrates beneficial effects in several clinical or preclinical models. Recent research on implementing novel combinatorial strategies also provides a positive outlook. These new strategies mainly focus on exploiting a cancer cell's context and tissue-specific fatty acid requirements.
This research topic focuses on emerging antitumor therapeutic strategies targeting fatty acid metabolism. We welcome submissions focused on:
• Clinical or preclinical targeting of fatty acid synthesis, desaturation, uptake, activation, oxidation, or transport.
• Clinical or preclinical targeting of intracellular lipolysis, triglyceride synthesis, phospholipid modification, and upstream regulators of fatty acid metabolism
• Metabolic synthetic lethality, such as co-targeting multiple enzymes within fatty acid metabolism-related pathways to combat the plasticity of these pathways
• Devising strategies to make the fatty acid metabolism-related pathways less dispensable for cancer cell survival by modulating the tumor microenvironment.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
