Existing and Developing Preclinical Models for Neurofibromatosis Type 1-Related Cutaneous Neurofibromas

Area of Science:

• Oncology
• Genetics
• Dermatology

Background:

• Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by the development of cutaneous neurofibromas (cNFs).
• The condition arises from a nonfunctional NF1 tumor suppressor gene, leading to the formation of numerous benign skin tumors.
• Understanding the pathophysiology and improving experimental models are crucial for developing effective NF1 treatments.

Purpose of the Study:

• To review the current state of preclinical in vitro and in vivo model systems for cutaneous neurofibromas (cNFs).
• To highlight the utility of these models in advancing the understanding of cNF biology and facilitating therapeutic discovery.
• To discuss the relationship between various experimental models and human cNFs.

Main Methods:

• Review of existing literature on preclinical models for NF1-associated cNFs.
• Discussion of various model systems including 2D/3D cell cultures, organoids, genetically engineered mouse models, patient-derived xenografts, and porcine models.
• Analysis of the strengths and limitations of each model in recapitulating human cNF development.

Main Results:

• Recent advances in preclinical modeling have significantly enhanced the understanding of cNF biology.
• A variety of in vitro and in vivo models are available, each offering unique insights into cNF pathogenesis.
• These models provide unprecedented opportunities for identifying and testing novel therapeutic strategies for cNFs.

Conclusions:

• Preclinical models are essential tools for unraveling the complexities of cNF development in Neurofibromatosis type 1.
• The discussed models offer valuable platforms for gaining insights into cNF pathophysiology.
• Continued development and application of these models are critical for advancing therapeutic discovery for cNFs.