Zebrafish Cancer Avatars: A Translational Platform for Analyzing Tumor Heterogeneity and Predicting Patient Outcomes.

The increasing number of available anti-cancer drugs presents a challenge for oncologists, who must choose the most effective treatment for the patient. Precision cancer medicine relies on matching a drug with a tumor's molecular profile to optimize the therapeutic benefit. However, current precision medicine approaches do not fully account for intra-tumoral heterogeneity. Different mutation profiles and cell behaviors within a single heterogeneous tumor can significantly impact therapy response and patient outcomes. Patient-derived avatar models recapitulate a patient's tumor in an animal or dish and provide the means to functionally assess heterogeneity's impact on drug response. Mouse xenograft and organoid avatars are well-established, but the time required to generate these models is not practical for clinical decision-making. Zebrafish are emerging as a time-efficient and cost-effective cancer avatar model. In this review, we highlight recent developments in zebrafish cancer avatar models and discuss the unique features of zebrafish that make them ideal for the interrogation of cancer heterogeneity and as part of precision cancer medicine pipelines.

An invertebrate model in examining the effect of acute ferric iron exposure on proprioceptive neurons.

Iron is an essential element for plant and animal life and is found in soil, fresh waters and marine waters. The Fe3+ ion is a vital prosthetic group and cofactor to mitochondrial electron transport complexes and numerous proteins involved in normal functioning. Despite its importance to life-sustaining processes, overexposure results in toxicity. For example, ferric iron (Fe3+) accumulation in the mammalian central nervous system is associated with various neurological disorders. Although current literature addresses the long-term effects of Fe3+ overload, fewer studies exist examining the effects of acute exposure. Using the blue crab (Callinectes sapidus), we investigate the effects of acute Fe3+ overload on proprioception within the propodite-dactylopodite (PD) nerve. For proprioceptive studies, 10- and 20-mM ferric chloride and ferric ammonium citrate solutions were used at 5- and 20- min exposure times. Exposure to 20 mM concentrations of ferric chloride and ferric ammonium citrate reduced excitability in proprioceptive neurons. Thus, Fe3+ likely blocks stretch-activated channels or voltage-gated Na+ channels. The depressive effects of Fe3+ are partly reversible following saline washout, indicating cells are not acutely damaged. Gadolinium (GdCl3, 1 and 10 mM) was used to examine the effects of an additional trivalent ion comparator. Gd3+ depressed PD nerve compound action potential amplitude while increasing the compound action potential duration. This study is relevant in demonstrating the dose-dependent effects of acute Fe3+ and Gd3+ exposure on proprioception and provides a model system to further investigate the mechanisms by which metals act on the nervous system.