Inducing hyperthermia in a tumor can allow treating physicians to enhance the effects of chemotherapy or achieve the same therapeutic outcome with lower doses of chemotherapy to minimize the treatment's adverse effects1.

Focused ultrasound can bolster the effects of chemotherapeutics in a number of ways. First, through the effects of local hyperthermia, greater concentrations of drugs can be delivered to tumors2. Second, the increase of blood flow due to the hyperthermia also increases the amount of oxygen delivered to the tumors. This increases the metabolic activity of the tumor cells and enhances the cytotoxicity of the drug3,4. In addition, it has been shown that cells that have acquired resistance to a particular drug can be made vulnerable again after ultrasound treatment1,5. Finally, local hyperthermia also weakens the tumor due to its reduced ability to dissipate heat, making the tumor more susceptible to chemotherapy yet leaving healthy tissue unaffected1,6.

Focused ultrasound provides a radiation-free, non-invasive method of inducing local hyperthermia7. The synergy between chemotherapy and focused ultrasound could allow for more effective chemotherapeutic treatments of cancer with diminished side effects8. Established methods of coupling hyperthermia with chemotherapy have been proven effective in preclinical work with ovarian and cervical cancer, however, this mechanism may be beneficial for any cancer that is responsive to chemotherapy6,9.

References:

[1] H. H. Kampinga, “Cell biological effects of hyperthermia alone or combined with radiation or drugs: a short introduction to newcomers in the field.,” Int. J. Hyperth. : Off. J. Eur. Soc. Hyperthermic Oncol. North Am. Hyperth. Group, vol. 22, no. 3, pp. 191–196, May 2006.

[2] Yuh EL, Shulman SG, Mehta SA, Xie J, Chen L, Frenkel V, et al. Delivery of systemic chemotherapeutic agent to tumors by using focused ultrasound: study in a murine model. Radiology. 2005;234:431–7.

[3] Song CW, Park HJ, Lee CK, Griffin R. Implications of increased tumor blood flow and oxygenation caused by mild temperature hyperthermia in tumor treatment. Int. J. Hyperth. Off. J. Eur. Soc. Hyperthermic Oncol. North Am. Hyperth. Group. 2005;21:761–7.

[4] Song CW, Shakil A, Osborn JL, Iwata K. Tumour oxygenation is increased by hyperthermia at mild temperatures. Int. J. Hyperth. Off. J. Eur. Soc. Hyperthermic Oncol. North Am. Hyperth. Group. 1996;12:367–73.

[5] Yu T, Li S, Zhao J, Mason TJ. Ultrasound: A Chemotherapy Sensitizer. Technol. Cancer Res. Treat. 2006;5:51–60.

[6] C. S. Muenyi, A. R. Pinhas, T. W. Fan, G. N. Brock, C. W. Helm, and J. C. States, “Sodium arsenite ± hyperthermia sensitizes p53-expressing human ovarian cancer cells to cisplatin by modulating platinum-DNA damage responses.,” Toxicol. Sci. : Off. J. Soc. Toxicol., vol. 127, no. 1, pp. 139–149, May 2012. 

[7] S. Wang, V. Frenkel, and V. Zderic, “Optimization of pulsed focused ultrasound exposures for hyperthermia applications.,” J. Acoust. Soc. Am., vol. 130, no. 1, pp. 599–609, Jul. 2011. 

[8] D. S. Finley, F. Pouliot, B. Shuch, A. Chin, A. Pantuck, J. B. Dekernion, and A. S. Belldegrun, “Ultrasound-based combination therapy: potential in urologic cancer.,” Expert Rev. Anticancer. Ther., vol. 11, no. 1, pp. 107–113, Jan. 2011. 

[9] Lee Y-Y, Cho YJ, Choi J-J, Choi CH, Kim T-J, Kim B-G, et al. The effect of high-intensity focused ultrasound in combination with cisplatin using a Xenograft model of cervical cancer. Anticancer Res. 2012;32:5285–9.
















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