The biology and treatment of leiomyosarcomas
William Kerrison, Khin Thway, Robin L. Jones, Paul H. Huang
Abstract
Leiomyosarcoma (LMS) is a soft tissue sarcoma of smooth muscle origin that can arise in multiple anatomical sites and is broadly classified as extra-uterine LMS or uterine LMS. There is substantial interpatient heterogeneity within this histological subtype, and despite multi-modal therapy, clinical management remains challenging with poor patient prognosis and few new therapies available. Here we discuss the current treatment landscape of LMS in both the localised and advanced disease setting. We further describe the latest advances in our evolving understanding of the genetics and biology of this group of heterogeneous diseases and summarise the key studies delineating the mechanisms of acquired and intrinsic chemotherapy resistance in this histological subtype. We conclude by providing a perspective on how novel targeted agents such as PARP inhibitors may usher in a new paradigm of biomarker-driven therapies that will ultimately impact the outcomes of patients with LMS. • Leiomyosarcomas encompass tumours of histological, clinical and molecular heterogeneity. • Despite multi-modal treatment, leiomyosarcoma patient outcomes are suboptimal. • The biology of drug resistance in leiomyosarcomas remains poorly understood. • PARP inhibitors are currently undergoing evaluation in uterine leiomyosarcoma.