To overcome the limitations of existing ablation techniques, we propose a novel combinatorial approach that would utilize the thermal and chemical destructive effects of exothermic chemical reactions, such as an acid/base neutralization reaction, to treat solid tumors. Thermochemical ablation is a potential technique for percutaneous probe-based tumor therapy. It involves simultaneous intratumoral delivery of multiple reagents resulting in thermal energy released by an exothermic reaction to ablate tumor tissue with concurrent generation of a hyperosmolar byproduct that could accentuate tumor destruction. Besides the benefit of synergistic thermal and chemical effects for tumor tissue destruction, this technique is potentially highly cost-effective, easy to implement, and able to treat larger sized tumors. Our hypothesis is that thermochemical ablation can create an evenly distributed zone of coagulation in tumor tissue without systemic toxicity. A prototype device assembled using off-the-shelf components is being investigated in our lab for concurrent intraparenchymal delivery of an acid and a base. The distal portion of the multi-lumen device allows for passive mixing of the reagents before entering the tissue. The prototype device also satisfies other desirable design criteria such as rigidity to penetrate body tissue, reduced diameter, chemical stability to reagents, etc. However, the device can be improved upon by incorporating additional characteristics such as optimized imaging characteristic for real-time visualization and localization within tumor tissue, MRI compatibility, thermal insulation, improved mixing at the tip, etc. Our lab is currently working on improving the design of the infusion device as well as assessing the feasibility of the thermochemical ablation technique in vitro and in vivo. While currently being targeted conservatively for palliative therapy of unresectable or late-stage aggressive malignancies such as hepatocellular carcinoma, thermochemical ablation has potential use in the therapy of a majority of solid tumors such as breast cancer, lung cancer, prostate cancer, renal cancer, sarcomas, etc.
Development of modulators of multidrug resistance: A pharmacoinformatic approach