Advanced biliary tract cancer represents one of the most challenging gastrointestinal malignancies in China, with increasing incidence and extremely poor prognosis due to late-stage diagnosis and limited treatment options. The integration of precision medicine approaches has transformed the therapeutic landscape by enabling personalized treatment strategies based on molecular profiling, tumor characteristics, and patient-specific factors. Recent developments encompass novel chemotherapy combinations, targeted therapies for specific genetic alterations, immunotherapy approaches, and emerging biomarkers that guide treatment selection and predict therapeutic responses.

The Warburg effect describes how cancer cells switch from oxidative phosphorylation to glycolysis even in oxygen-rich conditions, producing massive amounts of lactate that accumulate in the tumor microenvironment. This metabolic reprogramming creates an acidic milieu that suppresses immune function while fueling tumor growth and metastasis. Beyond serving as a waste product, lactate functions as a powerful signaling molecule that reshapes immune responses through multiple mechanisms, including direct receptor binding, transporter-mediated cellular reprogramming, and post-translational protein modifications known as lactylation.

Kyoto, Japan -- Aged and frail people often suffer a decline in tissue reserve capacity during aging. This reserve, called resilience, helps the body maintain homeostasis through various defense, compensation, modulation, and repair responses. When resilience is impaired, elderly people tend to experience a gradual waning of their daily activity and an increase in multimorbidity, or dealing with multiple chronic illnesses.

One major cause of resilience decline is an increase in senescent cells that have stopped dividing. The human body has a natural mechanism for eliminating these cells called senolysis, but as we age this 'clearing' mechanism becomes less efficient.

Senescent cells exert harmful effects through the senescence-associated secretory phenotype, or SASP: the release of pro-inflammatory molecules that can adversely affect surrounding cells. This leads to chronic inflammation and age-related diseases, partly explaining why elderly people suffer impaired resilience. Yet how metabolic resilience is involved in survival capacity and SASP has remained unclear.