Recent translational research into targeted therapy for liposarcoma

Rashi Bharat Patel, Ting Li, Zhichao Liao, Jivani Aakash Jaldeepbhai, H. A. Pavanika N. V. Perera, Sujani Kaushalya Muthukuda, Dholiya Hardeep Dhirubhai, Vaibhav Singh, Xiaoling Du, Jilong Yang


Liposarcomas (LPS) are among the most common soft tissue sarcomas, originating from adipocytes. Treatment for LPS typically involves surgical resection and radiation therapy, while the use of conventional cytotoxic chemotherapy for unresectable or metastatic LPS remains controversial. This review summarizes the results of recent translational research and trials of novel therapies targeting various genetic and molecular aberrations in different subtypes of LPS. Genetic aberrations such as the 12q13-15 amplicon, genetic amplification of MDM2, CDK4, TOP2A, PTK7, and CHEK1, point mutations in CTNNB1, CDH1, FBXW7, and EPHA1, as the fusion of FUS-DDIT3/EWSR1-DDIT3 are involved in the pathogenesis LPS and represent potential therapeutic candidates. Tyrosine kinase inhibitors targeting MET, AXL, IGF1R, EGFR, VEGFR2, PDGFR-β and Aurora kinase are effective in certain types of LPS. Abnormalities in the PI3K/Akt signaling pathway deregulation of C/EBP-α and its partner PPAR-γ, and the interaction between calreticulin (CRT) and CD47 are also promising therapeutic targets. These promising new approaches may help to supplement existing treatments for LPS.