Abstract
Cancer pain, a highly prevalent and distressing symptom among cancer patients, has a seriously harmful effect on their life and presents a complex challenge in clinical management. Despite extensive research efforts and the existence of clinical guidelines, significant controversies persist regarding the molecular mechanisms underpinning cancer pain as well as the most effective management strategies. This review systematically delves into the neurobiological underpinnings of cancer pain, centering on the interplay of peripheral and central sensitization, cellular stress and dysfunction, as well as the crucial roles of various signaling pathways and epigenetic regulation in its pathogenesis. In terms of treatment, the fundamental strategy involves a comprehensive initial assessment of cancer pain, followed by targeted interventions based on the assessment findings. It advocates for a multimodal approach that integrates pharmacological with non-pharmacological therapies. However, ongoing debates surround issues related to opioid rotation protocols and the long-term safety of opioid use. Furthermore, it underscores the underexplored potential of personalized therapies targeting molecular pathways and the need for standardized, interdisciplinary pain assessment tools. By bridging mechanistic research and clinical practice, this work potentially provides a framework for refining guideline implementation, advancing targeted therapies, and improving patient-centered care, thereby contributing to the evolution of precision oncology and holistic pain management paradigms.