Regulated nucleo-cytoplasmic transport plays a major role in maintaining cellular homeostasis. CRM1 (chromosome region maintenance 1 or exportin 1 or XPO 1) is responsible for the nucleo-cytoplasmic transport of more than 200 proteins, including most of the tumor suppressor proteins (TSP). CRM1 is overexpressed in pancreatic cancer, osteosarcoma, glioma, cervical and hematological malignancies. This inspired the development of novel agents that selectively inhibit nuclear exportins (SINEs). In this review we focus on the significance of CRM1 in carcinogenesis and review the new development of SINE inhibitiors in hematological malignancies. Selinexor (KPT-330) as the first-in-human SINE agent represents this novel class of anti-cancer agents.

SCLC remains an aggressive, deadly cancer with only modest effect on survival from standard chemotherapy. However, with the advent of immunotherapy and comprehensive genomic and transcriptomic profiling, multiple new targets are showing promise in the clinical arena, and just recently programmed death ligand 1 inhibition has been shown to improve the efficacy of standard chemotherapy in extended-disease SCLC. Our increasing understanding of the interactions between different pathways will enable more tailored immunotherapy and targeted therapies based on specific biomarkers and rational combinations. Here we discuss the preclinical and clinical strides in 2017 and 2018 that put us on the threshold of a new era in therapeutics and will, it is hoped, translate into significant improvements in survival.

Target specific oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) are changing the landscape of anticoagulation. The major drawback is the absence of an effective antidote for severe bleedings and/or prior to procedures. Currently there are a few promising antidotes undergoing clinical trials. This review summarized the latest development in idarucizumab, andexanet alpha and PER977.

Combretastatin A4 is a natural stilbenoid phenol derived from South African Bushwillow (Combretum caffrum). Combretum albidum, Crombretum densiflorum and Combretum roxburghii (Family: Combretaceae) are the unexplored medicinal plant in the Indian medicinal system. According to ethno-botanical information, the leaves, barks and fruits Combretum species have antimicrobial and anti-tumor activities and extensively used in the treatment of syphilis, abdominal pains, conjunctivitis, diarrhoea, toothache, peptic ulcer, dysentery, Jaundice, skin, heart and cancer diseases. The present study was undertaken to ascertain the presence of anticancer phyto-constituent in the Indian Combretum species and its further utilization in the treatment of tumor. The phyto-chemical constituents of the leaf and bark extracts were recognized with reference to standard on the same HPTLC plate. The leaf extracts exhibited higher quantity of combretastatins than the bark samples. The combretastatin content was recorded the highest (182 µg/g) in the leaf extract of C. albidum. Antibacterial activity was studied by disk diffusion assay against seven bacterial strains. The leaf extract of C. densiflorum resulted higher level of zone of inhibition against Bacillus subtilis (19 mm), Escherichia coli (18 mm), Salmonella enteric (18 mm), Streptococcus pneumoniae (16 mm), Staphylococcus aurius (13 mm), Pseudomonas aeruginosa (12 mm) and Mycococcus luteus (12 mm). Lower antimicrobial activities were recorded by the leaf and bark extracts of C. albidum. The carcinogenic effect of methanolic crude extracts on Allium cepa cells inducing chromosomal aberrations like chromosomal clumping, sticky bridge, laggard, early separation, late separation, chromosome break (fragmentation) and erosion (heavy fragmentation) were recorded. The methanolic leaf extract of Combretum albidum exhibited the highest percentage of chromosomal aberration such as sticky bridge in metaphase which demonstrated the strongest cytotoxic effect in the root meristem cells. These results suggest that the methanolic extract of Combretum species has antimicrobial and cytotoxic activities that support the ethano-pharmacological and anti-tumor uses of these plants.