Trends in clinical use of targeted therapy for gastrointestinal cancers

Targeted drugs therapies that block the molecular pathways involved in the development and progression of gastro-intestinal(GI)cancers have recently gained considerable attention.In addition to agents targeting vascular endothelial growth factor(VEGF),epidermal growth factor receptor,the multi-kinase inhibitor,and regorafenib have also become available for the treatment of metastatic colorectal cancer patients.Currently,trastuzumab,an antibody targeting human epidermal growth factor receptor-2(HER-2),in combination with cytotoxic drugs is considered as the standard treatment for patients with HER-2 positive gastric cancer(GC).The efficacy of ramucirumab,a human monoclonal antibody that inhibits VEGF from binding to its receptor in GC,has also been recently demonstrated.At present,a great number of novel targeted drugs are in pre-clinical or clinical studies.In this review,we summarize trends in the use of molecularly targeted drugs that have proven to be effective for treating GI cancers,with a focus on emerging strategies for personalized treatment.

Transferrin-guided intelligent nanovesicles augment the targetability and potency of clinical PLK1 inhibitor to acute myeloid leukemia

Acute myeloid leukemia(AML)remains a most lethal hematological malignancy,partly because of its slow development of targeted therapies compared with other cancers.PLK1 inhibitor,volasertib(Vol),is among the few molecular targeted drugs granted breakthrough therapy status for AML;however,its fast clearance and dose-limiting toxicity greatly restrain its clinical benefits.Here,we report that transferrin-guided polymersomes(TPs)markedly augment the targetability,potency and safety of Vol to AML.Vol-loaded TPs(TPVol)with 4%trans-ferrin exhibited best cellular uptake,effective down-regulation of p-PLK1,p-PTEN and p-AKT and superior apoptotic activity to free Vol in MV-4-11 leukemic cells.Intravenous injection of TPVol gave 6-fold higher AUC than free Vol and notable accumulation in AML-residing bone marrow.The efficacy studies in orthotopic MV-4-11 leukemic model demonstrated that TPVol significantly reduced leukemic cell proportions in periphery blood,bone marrow,liver and spleen,effectively enhanced mouse survival rate,and impeded bone loss.This transferrin-guided nano-delivery of molecular targeted drugs appears to be an interesting strategy towards the development of novel treatments for AML.

Management of metastatic esophagogastric junction adenocarcinoma

The prognosis of metastatic disease of esophagogastric junction adenocarcinoma remains poor,despite using a variety of regimens using cytotoxic agents.Recent understanding of molecular characteristic and tumor microenvironment of this cancer is currently instigating new therapeutic options.In this review,we summarized previous evidences of cytotoxic agents widely used worldwide,and updated recent developments of molecular targeted drugs,and immune checkpoint inhibitors.