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Hyperthermia (Hprt)

Hyperthermia (Hprt) in Oncology: Mechanisms, Applications, and Clinical Evidence

Hyperthermia (Hprt), a therapeutic approach that elevates tissue temperatures (typically 40–45°C), is increasingly used in oncology to enhance the efficacy of radiation and chemotherapy while directly damaging cancer cells. Its ability to exploit tumor vulnerabilities makes it a valuable adjunct in multimodal cancer treatment.

Mechanisms of Action

1. Enhanced Blood Flow:
   • Increases tumor perfusion, improving oxygen/nutrient delivery and radiosensitivity while enabling better drug penetration14.
2. Direct Cytotoxicity:
   • Temperatures >42°C disrupt cancer cell membranes, proteins, and DNA, triggering apoptosis23.
3. Synergy with Therapies:
   • Radiation: Hypoxic tumor regions (resistant to radiation) become oxygenated under heat, boosting radiation damage13.
   • Chemotherapy: Heat increases cell membrane permeability, enhancing uptake of chemotherapeutic agents14.
4. Immune Modulation:
   • Induces heat shock proteins (HSPs), which may stimulate anti-tumor immune responses but also promote thermotolerance26.

Types of Hyperthermia

Type	Application	Examples
Local Hyperthermia	Targets small tumors (e.g., skin, breast) using probes, microwaves, or ultrasound.	Superficial tumors, recurrent melanoma14.
Regional Hyperthermia	Heats larger areas (e.g., organs, limbs) via perfusion or deep-tissue devices.	HIPEC (heated intraperitoneal chemo) for abdominal cancers45.
Whole-Body Hyperthermia	Raises core body temperature (rare due to risks like cardiovascular strain).	Experimental for metastatic disease16.

Clinical Applications

1. Solid Tumors:
   • Breast Cancer: Combined with radiation, improves locoregional control3.
   • Cervical Cancer: Boosts radiation response, reducing recurrence3.
   • Soft Tissue Sarcomas: Enhances tumor resectability when used preoperatively3.
2. Peritoneal Cancers:
   • HIPEC delivers heated chemotherapy directly to the abdomen post-surgery, extending survival in ovarian/colorectal cancers5.
3. Melanoma/Sarcoma:
   • Isolated limb perfusion with heated chemotherapy preserves limbs in advanced cases5.

Combination Therapies

• Chemoradiation: Hyperthermia sensitizes tumors, allowing lower radiation/chemo doses and reducing side effects13.
• Immunotherapy: Emerging research explores pairing hyperthermia with checkpoint inhibitors to amplify immune responses27.

Adverse Effects

• Localized: Burns, blistering, or pain at the treatment site16.
• Regional/Whole-Body: Swelling, blood clots, or systemic inflammation14.

Challenges and Future Directions

1. Temperature Control: Precision heating remains technically challenging; nanoparticle-mediated hyperthermia (e.g., magnetic nanoparticles) improves targeting7.
2. Overcoming Thermotolerance: HSP inhibitors (e.g., quercetin) are being tested to counteract cancer cell resistance2.
3. Standardization: Lack of uniform protocols for heating duration/frequency13.

Conclusion

Hyperthermia is a versatile, cost-effective adjunct in oncology, enhancing traditional therapies through thermal sensitization and direct tumor damage. While clinical trials confirm its benefits in specific cancers (e.g., cervical, sarcoma), advancements in targeted delivery and combination strategies are critical to broadening its utility.

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References

1. Hyperthermia Therapy (Wikipedia)
2. Hyperthermia as Anti-Cancer Strategy (PMC)
3. Hyperthermia in Oncology (PMC)
4. NCI Guide to Hyperthermia
5. Cancer.org on Hyperthermia
6. Cleveland Clinic Overview
7. Nanoparticle-Mediated Hyperthermia (MDPI)