Defeating cancers’ adaptive defensive strategies using thermal therapies: Examining cancer’s therapeutic resistance, ablative, and computational modeling strategies as a means for improving therapeutic outcome

Abstract

Background: Diverse thermal ablative therapies are currently in use for the treatment of cancer. Commonly applied with the intent to cure, these ablative therapies are providing promising success rates similar to and often exceeding “gold standard” approaches. Cancer-curing prospects may be enhanced by deeper understanding of thermal effects on cancer cells and the hosting tissue, including the molecular mechanisms of cancer cell mutations, which enable resistance to therapy. Furthermore, thermal ablative therapies may benefit from recent developments in computer hardware and computation tools for planning, monitoring, visualization, and education. Methods: Recent discoveries in cancer cell resistance to destruction by apoptosis, autophagy, and necrosis are now providing an understanding of the strategies used by cancer cells to avoid destruction by immunologic surveillance. Further, these discoveries are now providing insight into the success of the diverse types of ablative therapies utilized in the clinical arena today and into how they directly and indirectly overcome many of the cancers’ defensive strategies. Additionally, the manner in which minimally invasive thermal therapy is enabled by imaging, which facilitates anatomical features reconstruction, insertion guidance of thermal probes, and strategic placement of thermal sensors, plays a critical role in the delivery of effective ablative treatment. Results: The thermal techniques discussed include radiofrequency, microwave, high-intensity focused ultrasound, laser, and cryosurgery. Also discussed is the development of thermal adjunctive therapies—the combination of drug and thermal treatments—which provide new and more effective combinatorial physical and molecular-based approaches for treating various cancers. Finally, advanced computational and planning tools are also discussed. Conclusion: This review lays out the various molecular adaptive mechanisms—the hallmarks of cancer—responsible for therapeutic resistance, on one hand, and how various ablative therapies, including both heating-and freezing-based strategies, overcome many of cancer’s defenses, on the other hand, thereby enhancing the potential for curative approaches for various cancers.