ROS proto-oncogene 1 (ROS1) rearrangements are reported in about 1–2% of non-squamous non-small-cell lung cancer (NSCLC). After efficacy of crizotinib was demonstrated, identification of ROS1 translocations in advanced disease became fundamental to give patients the chance of specific and effective treatment. Different methods are available for detection of rearrangements, and probably the real prevalence of ROS1 rearrangements is higher than that reported in literature, as our capacity to detect gene rearrangements is improving. In particular, with next generation sequencing (NGS) techniques, we are currently able to assess multiple genes simultaneously with increasing sensitivity. This is leading to overcome the “single oncogenic driver” paradigm, and in the very near future, the co-existence of multiple drivers will probably emerge more frequently and represent a therapeutic issue. Since recently, crizotinib has been the only available therapy, but today, many other tyrosine kinase inhibitors (TKI) are emerging and seem promising both in first and subsequent lines of treatment. Indeed, novel inhibitors are also able to overcome resistance mutations to crizotinib, hypothesizing a possible sequential strategy also in ROS1-rearranged disease. In this review, we will focus on ROS1 rearrangements, dealing with diagnostic aspects, new therapeutic options, resistance issues and the coexistence of ROS1 translocations with other molecular alterations.

Despite the introduction of novel therapeutic options, the prognosis of advanced endometrial cancer remains poor. In recent years, increasing attention has been directed toward the molecular characterization of endometrial cancer. However, data specifically focusing on advanced-stage disease are still limited. In our single-center, retrospective, exploratory study with a limited sample size, we analyzed 32 patients with advanced or recurrent endometrial cancer treated at the Modena Cancer Center. Comprehensive molecular profiling was performed to assess DNA mutations, copy number variations, and RNA expression. We characterized the molecular landscape of this cohort, evaluated selected genomic alterations across predefined clinical subgroups, and explored their association with overall survival. Consistent with previous reports, a high prevalence of PTEN and PIK3CA mutations were observed. Patients experiencing relapse more than six months after diagnosis were more likely to harbor CTNNB1 mutations. KRAS mutations were more frequently detected in younger patients and in those with endometrioid histology, whereas PPP2R1A and TP53 mutations were enriched in tumors with non-endometrioid histology. Notably, CTNNB1 mutations were associated with a favorable prognostic impact, while KRAS mutations correlated with poorer overall survival. Our findings underscore the need for further investigation into the molecular landscape of advanced endometrial cancer, particularly in the context of therapeutic implications. Combinatorial treatment strategies targeting specific molecular alterations, such as KRAS, in combination with other targeted agents or therapeutic approaches, warrant further exploration.