Advances and applications of hyperthermia in tumor therapy: Mechanisms, techniques, and clinical integration

Abstract

Hyperthermia (HT) has surfaced as a compelling supplementary approach in cancer treatment, owing to its capacity to selectively trigger cell death in tumors and amplify the efficacy of additional therapies. This review examines the most recent progress in hyperthermia methods, encompassing radiofrequency, microwave, focused ultrasound, and innovative approaches enhanced by nanotechnology, such as nano-photo-thermal therapy and nano-magnetic hyperthermia. Each approach utilizes distinct heat-induced mechanisms to directly target tumor cells or modify the tumor microenvironment, influencing aspects such as blood flow, oxygen availability, and the activity of immune cells. The modifications can enhance the effectiveness of chemotherapy and radiotherapy, in addition to emerging immunotherapies such as immune checkpoint inhibitors (ICIs), by leveraging synergistic and immune-activating mechanisms. We investigate the biological foundations of cell death caused by hyperthermia, which encompasses direct thermal injury as well as immunogenic reactions that include damage-associated molecular patterns (DAMPs) and promote the activity of natural killer (NK) cells within the tumor microenvironment (TME). Furthermore, we explore the clinical applications of hyperthermia in different cancer types, focusing on the safety and effectiveness of these approaches, as well as the latest technological innovations that aim to overcome challenges like the heat-sink effect. In conclusion, we present prospective avenues for advancement in hyperthermic tumor ablation, emphasizing enhancements in device technology and the synergy with combination therapies to optimize therapeutic outcomes. This review seeks to deliver an in-depth exploration of the mechanisms behind hyperthermia, its present clinical applications, and its capacity to revolutionize cancer treatment via cutting-edge, multimodal strategies.