The Power of Fish Models to Elucidate Skin Cancer Pathogenesis and Impact the Discovery of New Therapeutic Opportunities

Abstract

Animal models play important roles in investigating the pathobiology of cancer, identifying relevant pathways, and developing novel therapeutic tools. Despite rapid progress in the understanding of disease mechanisms and technological advancement in drug discovery, negative trial outcomes are the most frequent incidences during a Phase III trial. Skin cancer is a potential life-threatening disease in humans and might be medically futile when tumors metastasize. This explains the low success rate of melanoma therapy amongst other malignancies. In the past decades, a number of skin cancer models in fish that showed a parallel development to the disease in humans have provided important insights into the fundamental biology of skin cancer and future treatment methods. With the diversity and breadth of advanced molecular genetic tools available in fish biology, fish skin cancer models will continue to be refined and expanded to keep pace with the rapid development of skin cancer research. This review begins with a brief introduction of molecular characteristics of skin cancers, followed by an overview of teleost models that have been used in the last decades in melanoma research. Next, we will detail the importance of the zebrafish (Danio rerio) animal model and other emerging fish models including platyfish (Xiphophorus sp.), and medaka (Oryzias latipes) in future cutaneous malignancy studies. The last part of this review provides the recent development and genome editing applications of skin cancer models in zebrafish and the progress in small molecule screening.

Zebrafish Models of Cancer—New Insights on Modeling Human Cancer in a Non-Mammalian Vertebrate

“…It was shown that the genetic hybrids of the pigmented platyfish ( Xiphophorus maculatus ) and the non-pigmented swordtails ( Xiphophorus helleri ) spontaneously develop melanoma. This model is one of the earliest animal cancer models [10,11]. Another example is medaka ( Oryzias latipes ), a small freshwater fish which has helped to uncover new aspects of cancerogenesis, again mostly in melanoma pathogenesis [10,12].…”

“…This model is one of the earliest animal cancer models [10,11]. Another example is medaka ( Oryzias latipes ), a small freshwater fish which has helped to uncover new aspects of cancerogenesis, again mostly in melanoma pathogenesis [10,12]. Zebrafish ( Danio rerio ) has gained the most attention as a robust animal for studying development and disease.…”

Unique morphology and mechanical property of Chinese sturgeon (Acipenser sinensis) fish skin

“…The extracted gelatins from fish skin are the main ingredients of the gelatin films which are considered as a new environmentally friendly material [1][2][3]. Fish skin is also typically used as an effective drug-screening biological model, enabling us to deeply understand the human skin cancer [4][5][6]. Furthermore, for most fish species, their skins are covered by a large number of fish scales.…”

Mastomys Species as Model Systems for Infectious Diseases

“…Researchers introduced a plethora of animal models, such as zebrafish, rabbits, rats, dogs, pigs, goats, cattle and monkeys [ 22 , 23 , 24 , 25 , 26 ]. To be accepted as a valuable preclinical model, however, a scoring system should guarantee their careful selection, by reflecting face validity, complexity and predictability of a disease [ 27 , 28 ].…”