Bone sarcomas are a heterogeneous group of rare tumors with a predominance in the young population. Few options of systemic treatment are available once they become unresectable and resistant to conventional chemotherapy. A better knowledge of the key role that tyrosine kinase receptors (VEGFR, RET, MET, AXL, PDGFR, KIT, FGFR, IGF-1R) may play in the pathogenesis of these tumors has led to the development of multi-target inhibitors (TKIs) that are progressively being incorporated into our therapeutic arsenal. Osteosarcoma (OS) is the most frequent primary bone tumor and several TKIs have demonstrated clinical benefit in phase II clinical trials (cabozantinib, regorafenib, apatinib, sorafenib, and lenvatinib). Although the development of TKIs for other primary bone tumors is less advanced, preclinical data and early trials have begun to show their potential benefit in advanced Ewing sarcoma (ES) and rarer bone tumors (chondrosarcoma, chordoma, giant cell tumor of bone, and undifferentiated pleomorphic sarcoma). Previous reviews have mainly provided information on TKIs for OS and ES. We aim to summarize the existing knowledge regarding the use of TKIs in all bone sarcomas including the most recent studies as well as the potential synergistic effects of their combination with other systemic therapies.
Metastatic colorectal cancer (mCRC) with mutated BRAF exhibits distinct biological and molecular features that set it apart from other subtypes of CRC. Current standard treatment for these tumors involves a combination of chemotherapy (CT) and VEGF inhibitors. Recently, targeted therapy against BRAF and immunotherapy (IT) for cases with microsatellite instability (MSI) have been integrated into clinical practice. While targeted therapy has shown promising results, resistance to treatment eventually develops in a significant portion of responsive patients. This article aims to review the available literature on mechanisms of resistance to BRAF inhibitors (BRAFis) and potential therapeutic strategies to overcome them.
Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in patients with cancer. The management of special situations—including recurrent venous thromboembolism (VTE), thrombosis at unusual sites, and central venous catheter-associated thrombosis (CVC-AT)—remains particularly challenging because of the limited availability of high-quality evidence. This narrative review synthesizes recommendations from major international and Spanish clinical practice guidelines and expert consensus documents, including those from SEOM, ESMO, ASCO, NCCN, ITAC and SEMI, to provide a structured framework for the management of these complex scenarios. Our analysis identified substantial heterogeneity across guidelines, particularly regarding anticoagulant selection, dosing strategies, and treatment duration. Although some convergence exists in the management of CVC-AT, important discrepancies and evidence gaps persist in areas such as splanchnic vein thrombosis, hepatic impairment, central nervous system involvement, and recurrent VTE despite treatment. In many cases, recommendations are based primarily on expert opinion rather than robust trial data, and several clinical scenarios are addressed by only a limited number of guidelines. These findings underscore the need for more standardized management strategies and prospective clinical studies to better inform decision-making in daily practice. Overall, this review highlights the growing importance of individualized anticoagulant management aimed at balancing thrombotic and bleeding risks in high-risk oncology patients, thereby helping to bridge the gap between expert consensus and evidence-based precision anticoagulation.