Summary After curative intent resection, modified FOLFIRINOX is the standard of care in adjuvant in fit patients with PDAC. Others regimens (monotherapy or gemcitabine-based) are an option in unfit patients.Purpose of review Surgery represents the only curative approach for resectable gastric cancer. However, rates of recurrence remain high. This review summarizes the state of the art and future perspectives regarding perioperative, neoadjuvant and adjuvant chemotherapy for localized gastric cancer with insights regarding precision medicine. Recent findings Perioperative chemotherapy with FLOT has significantly improved outcomes for non-Asian patients with resectable gastric cancer, removing the role for anthracyclines. Preliminary results demonstrate that the perioperative approach is an option for Asian patients; however, long-term outcomes are awaited. For adjuvant treatment in Asian gastric cancer patients, S-1 as well as docetaxel may be a new treatment option. In this context, the right selection of patients is crucial. Among several biomarkers, microsatellite instability/mismatch repair deficiency has been linked with a lack of benefit from chemotherapy as well as better prognosis. Summary Multimodality treatment represents the standard of care for resectable gastric cancer. Perioperative chemotherapy with FLOT is the standard treatment in western countries; in patients who are not suitable for triplet, a platinum-fluoropyrimidine doublet can be considered. In Asian countries, adjuvant chemotherapy based on fluoropyrimidine monotherapy or in association with oxaliplatin/docetaxel are options. Validation of prognostic and predictive biomarkers is needed in order to improve patient selection.Purpose of review First clinical trials investigating immune check point (ICP) inhibitors in patients with sarcoma, regardless histological or molecular subtypes did not demonstrate any prolonged benefit. To maximize the chance of benefit from immunotherapy, recent strategies explore the combination of treatments and aim to improve identification of responsive histological subtypes. Recent findings Combination of several ICP inhibitors tends to increase toxicity and efficacy. Mechanisms of synergistic action remain unclear. Combination of ICP blockade with tyrosine kinase inhibitor increases efficacy in specific histological subtypes already identified as sensitive to each drug separately. The role of the combination is not established yet. Several ongoing trials assess the combination of ICP blockade with chemotherapy or radiotherapy. ICP blockade seems highly effective in some selected histological subtypes like alveolar soft part sarcoma, chordoma, malignant rhabdoid tumor, and angiosarcoma. Encouraging preliminary results need to be confirmed in larger cohorts and biological mechanisms that sustain this efficacy should be further explored. Adoptive cell therapy seems very promising in synovialosarcoma. Summary Significant efforts are underway to efficiently develop immunotherapy in patients with sarcoma and better characterize patients who would benefit the most from it.Purpose of review Giant cell tumour of bone (GCTB) is an intermediate, locally aggressive primary bone tumour. In addition to local therapy, new drugs became available for this disease. Denosumab, a receptor activator of nuclear factor κ-B-ligand inhibitor, was introduced as systemic targeted therapy for advanced or inoperable and metastatic GCTB. Also, the bisphosphonate zoledronic acid has activity in GCTB by directly targeting the neoplastic stromal cells. Recent findings In a small RCT, bisphosphonates were successful in controlling tumour growth and a higher apoptotic index of tumour cells was seen after zoledronic acid versus controls. Although bisphosphonate-loaded bone cement has not been studied to a large extent, it does not seem harmful and may constitute a logical local adjuvant. From the largest clinical trial to date, the risk-to-benefit ratio for denosumab in patients with advanced GCTB remains favourable, also in facilitating less morbid surgery. Concerns have arisen that recurrence rates woulher research on bisphosphonates and other targets including H3.3-G34W remains warranted.Purpose of review Sarcomas are a diverse group of rare solid tumors with limited treatment options for patients with advanced, inoperable disease. Cabozantinib is a tyrosine kinase inhibitor currently approved for advanced renal cell, hepatocellular, and medullary thyroid carcinoma. Cabozantinib has potent activity against a variety of kinases, including MET, vascular endothelial growth factor receptor, and AXL, that are associated with sarcoma growth and development. Here we review the preclinical findings and clinical development of cabozantinib in the treatment of soft tissue sarcoma, gastrointestinal stromal tumors (GIST), osteosarcoma, and Ewing sarcoma. Recent findings In vitro, cabozantinib has shown relevant activity in inhibiting the growth and viability of soft tissue sarcoma, GIST, osteosarcoma, and Ewing sarcoma tumor cell lines. Cabozantinib also promoted the regression of GIST in various murine xenografts, including imatinib-resistant models. More than 10 prospective trials with cabozantinib that included patients with sarcomas have been completed or are currently ongoing. https://www.selleckchem.com/products/way-309236-a.html Clinical activity with cabozantinib has been recently reported in phase 2 clinical trials for patients with GIST and for patients with osteosarcoma or Ewing sarcoma. Summary Cabozantinib has shown promising activity for the treatment of various sarcomas, supporting further evaluation in this setting.Purpose of review Tyrosine kinase inhibitors (TKIs) are the backbone for advanced gastrointestinal stromal tumor (GIST) treatment. The increasing knowledge concerning the structure and the changing conformational status because of some mutations in KIT and PDGFRα, allowed the development of new efficient compounds, with the main goal to overcome resistance in GIST. This review summarizes the latest developments in the treatment of GIST patients. Recent findings Amongst the several TKIs currently being studied in GIST, ripretinib, avapritinib and crenolanib had shown promising potent activity in preclinical studies and clinical trials. Ripretinib is a type II inhibitor that exerts its main action in the switch pocket of the activation loop, by mimicking the inhibition exerted by the regulatory region in this domain. Ripretinib is considered the new standard in the fourth line in advanced GIST. Avapritinib is a type I inhibitor synthesized to exerts its activity in the active conformation of the activation loop of KIT and PDFGRα.