Hyperthermic tumor microenvironment (HTM)

The hyperthermic tumor microenvironment is a physiological state in which tumor tissue is intentionally heated to temperatures between 40°C and 45°C to improve the efficacy of cancer therapies (National Cancer Institute, 2021). Although it is not a discrete molecular target like a receptor or enzyme, this environment acts as a physical trigger for advanced drug delivery systems, such as thermosensitive liposomes (e.g., ThermoDox), which are designed to release their therapeutic contents only when exposed to specific thermal thresholds (Needham & Dewhirst, 2001). Biologically, hyperthermia induces the heat shock response, increases local blood flow, and enhances vascular permeability, which facilitates the deep penetration of chemotherapeutic agents and improves oxygenation to combat hypoxia-driven treatment resistance (Issels, 2008). Furthermore, hyperthermia serves as a potent sensitizer for both radiotherapy and chemotherapy by disrupting DNA repair pathways and promoting cellular apoptosis (Horsman & Overgaard, 2007). Despite these advantages, the clinical use of hyperthermia is limited by the technical challenges of maintaining uniform temperature distribution and the potential for causing thermal damage to surrounding healthy tissues (Wust et al., 2002).

Other names

Heated tumor tissueHyperthermiaThermal tumor microenvironmentTumor hyperthermia

Hyperthermia enhances drug delivery by increasing tumor blood flow and vascular permeability, triggers drug release from stimuli-responsive nanocarriers, and sensitizes tumor cells to chemotherapy and radiation by inhibiting DNA repair mechanisms (Wust et al., 2002; Issels, 2008).