Drug Development Targeting Tumor Metabolism

The field of cancer research has increasingly focused on the metabolic underpinnings of tumorigenesis, recognizing how the reprogramming of cellular energy pathways fuels uncontrolled growth and survival. Tumor cells often display profound alterations in their metabolism compared to normal counterparts, allowing them to adapt to hostile microenvironments, resist apoptosis, and evade immune surveillance. While classical approaches to cancer treatment have concentrated on targeting proliferation and cell division, there is growing evidence that cancer cell metabolism represents a fundamental driver of malignancy and therapeutic resistance. A deeper understanding of metabolic adaptations—such as shifts in redox homeostasis, mitochondrial dynamics, and enzyme function—has begun to emerge, yet many aspects of metabolic transformation in cancer remain incompletely understood.
Recent studies have highlighted both the complexity and specificity of metabolic processes that are hijacked by tumors. Novel findings on mitochondrial alterations and enzyme dysfunctions have shed light on the diverse strategies tumor cells use to maintain their aberrant phenotype. Simultaneously, the identification of new chemical entities and natural compounds that selectively disrupt cancer metabolism has paved the way for innovative therapeutic options. However, significant challenges persist, including the heterogeneity of tumor metabolism across cancer types and within the same tumor, the adaptability of metabolic networks, and the translation of preclinical successes into safe, effective patient therapies. There is a critical need for coordinated research efforts that dissect these metabolic dependencies, clarify their clinical significance, and harness them for drug discovery.

This Research Topic aims to advance our understanding of cancer cell metabolic reprogramming and its exploitation for drug development. The central objectives are to clarify the mechanisms driving metabolic transformation in tumors, investigate their contribution to oncogenesis and treatment resistance, and promote the discovery and preclinical development of novel treatments—both synthetic and natural—that target cancer metabolism. We particularly encourage research addressing how specific molecular pathways and metabolites can serve as therapeutic targets, the identification of biomarkers for patient stratification, and the evaluation of clinical challenges in this evolving domain.

To gather further insights into the boundaries of targeting tumor metabolism for therapeutic purposes, we welcome articles addressing, but not limited to, the following themes:
o The role of redox homeostasis in tumor progression
o The contribution of mitochondrial alterations to cancer development
o Dysfunction and regulation of metabolic enzymes in tumor cells
o The rational design and characterization of novel compounds with anticancer activity
o The exploration and development of natural compounds as anticancer agents
o Advances in metabolic pathway mapping and biomarker identification
o Clinical translation and challenges in targeting tumor metabolism


Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal.