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.

Evaluation of a Novel Cystoscopic Compatible Cryocatheter for the Treatment of Bladder Cancer

“…This is compared to argon JT based cryosystems where the -20 • C isotherm is reported to penetrate <5 mm in 2 mins and ∼9 mm following 5+ mins of freezing [44,51,52]. Depth of penetration of the -20 • C and -40 • C isotherms are often used as reference points clinically [1,8,9,16,17,22,23]. With the reported minimal lethal temperature for BC in the range of -20 • C, we focused on the -20 • C isotherm as it represents a potential target isotherm for the treatment of BC [46].…”

“…Importantly, cryolesions do not "grow" post treatment whereas heat-based lesions will increase in size (depth) for several days, clinically resulting in a higher risk of complications [11][12][13][14]. Other benefits include depth of penetration, ability to use in combination with other treatments (adjunctive role), likely improved hemostasis and the ability to target non-resectable tumors [15][16][17][18]. Through percutaneous needles or catheter-based approaches, the delivery of cryoablative doses to tissues not traditionally targeted by the therapy have expanded [19][20][21][22][23][24][25][26][27][28][29].…”

Mild hyperthermia by MR-guided focused ultrasound in an ex vivo model of osteolytic bone tumour: optimization of the spatio-temporal control of the delivered temperature

“…In addition to traditional approaches (surgery, radiotherapy and chemotherapy), thermal therapies are nowadays being increasingly recognized as treatment options for primary cancers, as well as for metastases [14]. In thermal ablation, heating of the tumour tissue to temperatures of about 55–60 °C for short time periods (typically less than 2 min) causes thermal denaturation of proteins and cell membranes, and results in cell death within minutes (via coagulative necrosis) or hours (via apoptosis).…”

“…To increase tissue temperatures, usually electromagnetic or ultrasound energy, such as radiofrequency waves (RF), microwaves (MW), laser, or high intensity focused ultrasound (HIFU), is directed at the target tissue. An interstitial or intracavitary antenna can be used for RF/MW, a fiber-optic probe is inserted into the tumour for laser therapy, while in cryoablation tissue freezing is performed via cryoprobes inserted into the tissue [14]. Though minimally invasive, these techniques are difficult to apply to bone tumours, since they require the insertion of a heat (or cold) source directly into bone tissue.…”

Sulforaphane-N-Acetyl-Cysteine Induces Autophagy Through Activation of ERK1/2 in U87MG and U373MG Cells

“…Autophagy is an important mechanism for maintaining cellular homeostasis through nutrition recycling and protein quality control. Further evidence has shown that autophagy may be activated during chemotherapy in most tumor cell lines [30]. Autophagy also plays a central role in pharmacological manipulation, and its pathways may serve as therapeutic targets for treating cancer [31].…”