Abstract
Simple Summary This review discusses current and prospective treatment strategies for retroperitoneal liposarcoma, a rare type of sarcoma with a high propensity for locoregional recurrence and low survival rate. Chemo- and radiotherapy regimens, as well as molecular targets, are highlighted as important tools to better explore the mechanisms underlying this disease and to pursue new possible targetable pathways. Liposarcoma (LPS) is the most prevalent soft tissue sarcoma histological subtype. When it occurs in the abdomen the overall survival rate is as low as 10% at 10 years and is fraught with high rates of recurrence, particularly for the more aggressive dedifferentiated subtype. Surgery remains the mainstay of treatment. Systemic therapies for the treatment of metastatic or unresectable disease have low response rates. Deep understanding of well-differentiated and de-differentiated LPS (WDLPS and DDLPS, respectively) oncologic drivers is necessary for the development of new efficacious targeted therapies for the management of this disease. This review discusses the current treatments under evaluation for retroperitoneal DDLPS and the potential targetable pathways in DDLPS.