Oncometabolites-driven tumorigenesis: From genetics to targeted therapy

Area of Science:

• Oncology
• Biochemistry
• Molecular Biology

Background:

• Alterations in cellular metabolism have long been associated with cancer, as first noted by Warburg.
• Recent discoveries of mutations in metabolic enzymes (e.g., succinate dehydrogenase, fumarate hydratase, isocitrate dehydrogenase) have renewed interest in cancer metabolism.
• These mutations are linked to various tumor types and susceptibility to cancer.

Purpose of the Study:

• To review the diverse pathways affected by oncometabolites.
• To discuss the role of oncometabolites in cancer formation, maintenance, and metastasis.
• To explore the impact of oncometabolites on chemotherapy sensitivity and emerging therapeutic strategies.

Main Methods:

• Literature review of studies on cancer metabolism and genetic mutations.
• Analysis of the biochemical mechanisms of oncometabolite action.
• Synthesis of information on therapeutic strategies targeting cancer metabolism.

Main Results:

• Mutations in metabolic enzyme genes lead to the accumulation of oncometabolites.
• Oncometabolites interfere with 2-oxoglutarate-dependent dioxygenases.
• Affected pathways include hypoxic response and epigenetic reprogramming.

Conclusions:

• Oncometabolites play a significant role in cancer development, progression, and metastasis.
• Understanding oncometabolite-driven pathways is crucial for developing novel cancer therapies.
• Targeting metabolic alterations presents promising new therapeutic avenues for cancer treatment.