Modeling Myxofibrosarcoma: Where Do We Stand and What Is Missing?

SIMPLE SUMMARY: Myxofibrosarcoma (MFS) is one of the most common malignant soft tissue sarcomas. MFS occurs mostly in the extremities of patients after the fifth decade of life as a painless a slow-growing mass. In most of the cases treatment is surgical resection of the tumor. However, at times surgeons can’t distinguish the boundaries of the tumor and are unable to remove all the tumor cells. Therefore, the tumor cells left in the patients can spread and grow again (recurrence). When MFS recurs more than once it is a challenge for clinicians and a burden for patients. Therefore, especially for patients that recur more than once new therapeutic approaches are needed. In vitro and in vivo models are helpful to understand the disease and to test new therapeutic agents. This review details the available MFS models, identifies critical issues of each model, and suggests models that would be useful to develop in the future. ABSTRACT: Myxofibrosarcoma (MFS) is a malignant soft tissue sarcoma (STS) that originates in the body’s connective tissues. It is characterized by the presence of myxoid (gel-like) and fibrous components and typically affects patients after the fifth decade of life. Considering the ongoing trend of increasing lifespans across many nations, MFS is likely to become the most common musculoskeletal sarcoma in the future. Although MFS patients have a lower risk of developing distant metastases compared with other STS cases, MFS is characterized by a high frequency of local recurrence. Notably, in 40–60% of the patients where the tumor recurs, it does so multiple times. Consequently, patients may undergo multiple local surgeries, removing the risk of potential amputation. Furthermore, because the tumor relapses generally have a higher grade, they exhibit a decreased response to radio and chemotherapy and an increased tendency to form metastases. Thus, a better understanding of MFS is required, and improved therapeutic options must be developed. Historically, preclinical models for other types of tumors have been instrumental in obtaining a better understanding of tumor development and in testing new therapeutic approaches. However, few MFS models are currently available. In this review, we will describe the MFS models available and will provide insights into the advantages and constraints of each model.