ENHANCED ETHANOL-BASED LOCOREGIONAL THERAPIES FOR TREATMENT OF SOLID TUMORS IN UNDERPRIVILEGED POPULATIONS

Abstract

Cancer is quickly becoming the leading cause of death globally, with an estimated 19.3 million new cancer cases and 9.9 million cancer deaths in 2020. While surgical resection of solid tumors, chemotherapy, or radiation are common methods for cancer management, a paucity of medical resources to perform the procedures prevent underprivileged cancer patient populations from receiving adequate treatment and care. Minimally invasive ablative therapies have the potential to address these issues and thus are crucial to addressing the increasing cancer burden in low- and middle-income countries. Ethanol ablation is one such low-cost treatment that directly injects ethanol into tumors to induce necrosis and is capable of treating nodules up to 3 cm in diameter. Intratumoral injections of ethanol into non-encapsulated tumors may, however, experience ethanol escape and leakage from the injection site, resulting in the need for multiple treatments and an increased risk of collateral damage to surrounding tissues. To mitigate this shortcoming, ethyl cellulose (EC) was dissolved in the injected ethanol to form a solid gel upon contact with the tumor environment, promoting ethanol retention within tumors and subsequently improving ablative efficiency and efficacy. The central hypothesis of this dissertation is that EC confers substantial biophysical enhancements to ethanol-based locoregional therapies that allow for improved cancer management strategies. This work explores the capabilities of EC-ethanol in treating solid tumors, which includes 1) pairing the technology with ultrasound to visualize its local distribution, 2) using it in tandem with photodynamic therapy to enhance locoregional tumor ablation of more advanced disease, and 3) investigating the local and systemic antitumoral effects of EC-ethanol to cause distant tumor regression. The results from this dissertation demonstrate the versatility of the EC-ethanol technology in treating a variety of solid tumors and can be built upon existing clinical workflows worldwide to improve cancer treatment outcomes for all patients.