Novel Approaches to Treatment of Leiomyosarcomas

Soft tissue sarcomas are rare tumors and include subtypes with variable clinical, pathological, and genetic characteristics, including leiomyosarcoma. Current chemotherapy options include the use of doxorubicin, ifosfamide, gemcitabine and docetaxel, and trabectedin, but these have poor response rates in the metastatic setting. While some targeted therapies with tyrosine kinase inhibitors have shown promise, there is a clear need for novel, targeted strategies for this enigmatic form of soft-tissue sarcoma. The genomic instability and multiple, complex karyotypic abnormalities of leiomyosarcomas is a potential for therapy with agents with proven activity in other cancers with genomic instability, such as BRCA-related breast or ovarian cancer. There are few pathways affected in leiomyosarcoma that suggest obvious opportunities, but poly ADP-ribose polymerase (PARP) inhibitors hold promise. This article outlines current therapeutic options available and undergoing study, as well as explores the rationale for the study of PARP inhibitors in leiomyosarcomas, with or without chemotherapy.