Navigating the New Therapeutic Landscape: Innovative Strategies for Overcoming Resistance and Degeneration

Recent technological advancements and environmental shifts have reshaped the therapeutic landscape of human diseases, driv-ing a transition from merely understanding pathogenesis to developing precise and targeted therapeutic solutions. While the 2025 Special Issue focused on identifying emerging risk factors, the 2026 Special Issue (Vol. 34, No. 1) pivots toward concrete method-ological innovations and advanced therapeutic interventions. This issue presents a curated collection of ten distinguished articles organized around three core themes. First, in the field of oncology and drug resistance, studies investigate transglutaminase 2 (TG2)-mediated autophagy and ferroptosis as strategies to overcome therapeutic resistance, alongside advances in CAR-T cell engineering and the integration of artificial intelligence (AI) with robotic surgery to enable precision medicine. Second, addressing degenerative and metabolic diseases, contributions elucidate the role of Wnt/β-catenin signaling in osteoporosis, recent therapeutic advances in knee osteoarthritis, mechanisms underlying drug-induced senescence, and the application of gene-editing technologies in iPSC-derived hepatic models. Finally, investigations into the neuro–immune axis highlight the dual roles of adaptive immunity in Alzheimer’s disease and evaluate novel pharmacological modulators targeting the kynurenine–aryl hydrocarbon receptor (AhR) axis. Collectively, this Special Issue delivers groundbreaking insights and innovative strategies aimed at restoring biological homeostasis and overcoming intractable diseases.