Expression and role of TYRO3 and AXL as potential therapeutical targets in leiomyosarcoma

Leiomyosarcoma (LMS) is a malignant tumour of the smooth muscle cells arising from soft tissues or viscera, including the uterine corpus, more rarely the bone (Brewer et al, 2012). Leiomyosarcoma represent 15% of adult sarcomas, and gather a heterogeneous group of tumours with different grades and presentation (Ducimetiere et al, 2010). Most LMS are high-grade sarcomas and exhibit a clinically aggressive behaviour (Clark et al, 2005; Toro et al, 2006). The metastatic relapse rate following local treatment is ~40% at 5 years (Trent et al, 2007), and cure rate in advanced phase remains very low (<5%) with current treatment options, including cytotoxics and targeted agents (Mir et al, 2016; Ratan and Patel, 2016). Cytogenetic analysis and CGH arrays reveal multiple chromosomal rearrangements, with molecular subclassifications emerging (Chibon et al, 2010). However, no strong driver genetic alteration has been identified so far in these diseases (Miettinen, 2014). Cytotoxic and targeted therapies, including pazopanib and trabectedin, prolong progression-free survival (Le Cesne et al, 2005; Benson et al, 2016), and eribulin improved overall survival (Schoffski et al, 2016). However, the median PFS is close 4 months with these different agents in LMS, with few long-term responders, and no key biomarker has been identified to guide the treatment (van der Graaf et al, 2012).