Cytostatic hypothermia and its impact on glioblastoma and survival

Abstract

Patients with glioblastoma (GBM) have limited options and require novel approaches to treatment. Here, we studied and deployed nonfreezing “cytostatic” hypothermia to stunt GBM growth. This growth-halting method contrasts with ablative, cryogenic hypothermia that kills both neoplastic and infiltrated healthy tissue. We investigated degrees of hypothermia in vitro and identified a cytostatic window of 20° to 25°C. For some lines, 18 hours/day of cytostatic hypothermia was sufficient to halt division in vitro. Next, we fabricated an experimental tool to test local cytostatic hypothermia in two rodent GBM models. Hypothermia more than doubled median survival, and all rats that successfully received cytostatic hypothermia survived their study period. Unlike targeted therapeutics that are successful in preclinical models but fail in clinical trials, cytostatic hypothermia leverages fundamental physics that influences biology broadly. It is a previously unexplored approach that could provide an additional option to patients with GBM by halting tumor growth.

Excessive Lipid Production Shapes Glioma Tumor Microenvironment

“…For example, lipomatous glioma brain tumors tend to be hypothermic or lower in temperature than the surrounding healthy tissues [ 26 ]. Some reports suggested treating glioma tumors with hypothermia [ 27 ]; however, an opposite trend is making headway to treat malignant glioma using hyperthermia [ 28 ]. We think that hyperthermia is probably more appropriate since it may strip the tumor and its cells from their protective fatty coat.…”

The natural origins of cytostatic compounds used in rhabdomyosarcoma therapy

“…Numerous natural products exhibit anti-cancer activities, including anti-proliferative, pro-apoptotic, antimetastatic, and anti-angiogenic effects, and also regulate autophagy, balance immunity, and enhance chemotherapy both in vitro and in vivo. 103,104 Since anti-cancer therapies are often limited by a low therapeutic index and cancer resistance to pharmacotherapy, it is very important to search for new, effective compounds. The most common mechanisms for the anti-cancer activity of these compounds include, but are not limited to, migration, proliferation and cell death pathways, such as apoptosis and autophagy.…”

Finite element analysis of a neural implant for cytostatic hypothermia and a novel heat management system

“…Regardless, that recurrence is close to the resection margin highlights the potential for local therapeutic interventions against recurrent GBM. Our prior work has elucidated the efficacy of local cytostatic hypothermia in prolonging survival in two rat GBM models [9]. We and others have identified that various tumor types exhibit cell division cessation at temperatures between 20-28°C [9], [10], [11], [12], [13], [14], [15], [16].…”

“…This approach not only demonstrates promising preclinical results but also holds translational potential, as the physical principles that undergird the strategy apply similarly to rodents and to humans. Nonetheless, a pivotal challenge lies in the design of a clinically relevant medical device [9], [17], [18], [19], [20], [21].…”

“…Our prior work has elucidated the efficacy of local cytostatic hypothermia in prolonging survival in two rat GBM models [9]. We and others have identified that various tumor types exhibit cell division cessation at temperatures between 20–28°C [9], [10], [11], [12], [13], [14], [15], [16]. This approach not only demonstrates promising preclinical results but also holds translational potential, as the physical principles that undergird the strategy apply similarly to rodents and to humans.…”