The Adipose–Tumor Axis: Unraveling How Fat Tissue Drives Cancer Progression and Shapes Therapeutic Response
核心洞察
Adipose tissue (搜索) is now recognized as a metabolically active organ that secretes adipokines and cytokines influencing tumor initiation, progression, and therapy response.
Obesity (搜索)-induced adipose tissue (搜索) dysfunction is linked to increased risk and poorer outcomes in at least a dozen cancer (搜索) types, though some cancers show a paradoxical benefit with immune checkpoint inhibitors.
White adipose tissue (搜索) fuels tumor growth through free fatty acid mobilization, while dysregulated adipokine signaling reshapes the tumor microenvironment.
The biological conversation between adipose tissue (搜索) and malignant cells is emerging as one of the most consequential yet incompletely understood dialogues in oncology. Once dismissed as a passive energy depot, adipose tissue is now recognized as a highly dynamic endocrine organ whose secreted factors—adipokines, cytokines, and free fatty acids—can fundamentally alter tumor biology. Two new Research Topics published in Frontiers highlight the urgent scientific effort to decode this adipose–tumor crosstalk and translate those insights into clinical interventions.
A paradigm shift in adipose biology
The traditional view of fat as inert storage has given way to a model of adipose tissue (搜索) as a metabolically active organ central to systemic metabolism and inter-organ communication. Through the secretion of bioactive molecules, adipose tissue engages in a molecular dialogue that supports normal physiology but, when dysregulated, can drive pathological states—most notably cancer (搜索). This dysfunction is particularly pronounced in obesity (搜索), where chronic inflammation and altered adipokine profiles create a microenvironment conducive to tumor initiation and progression.
White, brown, and beige adipose tissue (搜索) subtypes each display distinct functional profiles in the cancer (搜索) context. White adipose tissue, the predominant form, mobilizes free fatty acids and other nutrients that can directly fuel tumor growth and survival. Meanwhile, the dysregulated production of adipokines and cytokines characteristic of obesity (搜索) further activates tumor-promoting signaling cascades.
Obesity (搜索) as a cancer (搜索) risk modifier
Epidemiological studies have firmly established obesity (搜索) as a risk factor for at least a dozen cancer (搜索) types, and excess adiposity can also influence prognosis after diagnosis. Yet the relationship is not uniformly detrimental. Recent findings suggest that in select cancer subtypes, obesity may paradoxically improve outcomes and bolster responses to immune checkpoint inhibitors—a phenomenon that complicates clinical decision-making.
This paradox is further obscured by the widespread reliance on body mass index as a proxy for adiposity. BMI fails to capture critical variables such as adipose tissue (搜索) distribution and sarcopenic obesity (搜索), both of which may independently modulate tumor biology and treatment response. Resolving these ambiguities has become a priority for the emerging field of metabo-oncology, which sits at the intersection of oncology, metabolism, and obesity research.
Therapeutic horizons
Investigators are now exploring whether the adipose–tumor axis can be therapeutically targeted. Novel strategies under consideration include pharmacologic interventions such as GLP-1 (搜索) and GIP (搜索)-based incretin therapies, structured exercise regimens, and precision nutrition approaches. The goal is to integrate metabolic interventions with standard-of-care cancer (搜索) treatments to improve survival, remission rates, and patient quality of life.
Key research questions include defining why adiposity and related systemic factors influence the risk or progression of different malignancies variably, and how emerging biomarkers might enable personalized risk stratification and therapy selection. Both preclinical and clinical studies are being sought to bridge biological insight with translational advances.
Unresolved questions and future directions
Despite significant progress, many mechanistic details of adipose–tumor interactions remain poorly understood. There is a pressing need for integrative research that clarifies the precise contributions of adipose tissue (搜索) heterogeneity and its secretome to cancer (搜索) risk and progression. Research priorities include elucidating mechanisms by which different adipose subtypes influence tumor progression, characterizing metabolic crosstalk and lipid transfer in cancer cell survival, and defining the impact of obesity (搜索)-induced adipose dysfunction on therapy resistance.
Dr. Louise Lang Lehrskov, a topic editor, reports receiving speaker honoraria from Ipsen unrelated to the present work. The Research Topics explicitly note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic databases without independent cohort or biological validation fall outside their scope, underscoring the emphasis on mechanistic and translational rigor.