SciBX: Science-Business eXchange Contents: August 28 2014, Volume 7 / Issue 33

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TABLE OF CONTENTS August 28 2014, Volume 7 / Issue 33 Analysis Cover Story Translational Notes Targets and Mechanisms The Distillery: Therapeutics Cancer Cardiovascular disease Endocrine/metabolic disease Hematology Inflammation Neurology Pulmonary disease The Distillery: Techniques Markers Assays and screens Disease models Drug delivery Drug platforms   Cover Story Top Overcoming ibrutinib resistance Lauren Martz doi:10.1038/scibx.2014.971 The CDK4 inhibitor palbociclib might help overcome ibrutinib resistance in mantle cell lymphoma by restoring sensitivity to inhibitors of BTK or PI3K. Full Text | PDF Translational Notes Top Getting researchers off the grant treadmill Tracey Baas doi:10.1038/scibx.2014.972 The National Cancer Institute has created a generous seven-year award designed to ease the grant-writing burden for 'outstanding investigators'. Now the institute needs to ensure that the program is not just easier riches for the top labs but instead makes a difference for up-and-coming researchers. Full Text | PDF Industrial strength for Sanford-Burnham Kai-Jye Lou doi:10.1038/scibx.2014.973 GSK executive Perry Nisen has joined Sanford-Burnham as CEO and plans to apply his industry know-how to accelerate drug development at the institute. Full Text | PDF Targets and Mechanisms Top A cultured approach to ALS therapy Michael J. Haas doi:10.1038/scibx.2014.974 The mechanisms by which dysfunctional glial cells contribute to ALS have remained poorly defined. Now, Harvard University researchers have identified a therapeutic target—prostaglandin D2 receptor subtype DP1—and shown that reducing its expression can prolong survival in a mouse model of ALS. Full Text | PDF Distillery: Therapeutics Cancer Top MEK; notch 1 (NOTCH1); phosphoinositide 3-kinase (PI3K) doi:10.1038/scibx.2014.975 Mouse and cell culture studies suggest combined inhibition of PI3K and MEK could help treat T cell ALL, although it can also drive notch pathway–related resistance. Full Text | PDF CD3; C-type lectin domain family 12 member A (CLEC12A; CLL1) doi:10.1038/scibx.2014.976 Studies in patient samples, mice and cell culture suggest a bispecific antibody against CLL1 and CD3 could help treat AML. Full Text | PDF γ-aminobutyric acid A receptor-π (GABRP) doi:10.1038/scibx.2014.977 In vitro studies suggest inhibiting GABRP could help treat and prevent metastasis of basal-like breast cancers. Full Text | PDF Butyrophilin subfamily 3 member A1 (BTN3A1) doi:10.1038/scibx.2014.978 Cell culture studies suggest a pivaloyloxymethyl-protected phosphoantigen prodrug could help treat cancer. Full Text | PDF Casein kinase 1α (CSNK1A; CKI-α); sonic hedgehog homolog (SHH) doi:10.1038/scibx.2014.979 Mouse and cell culture studies suggest agonizing CKI-α could be useful for treating hedgehog pathway–driven cancers that have developed resistance to smoothened (SMO) inhibitors. Full Text | PDF DNA doi:10.1038/scibx.2014.980 Mouse studies have identified a class of platinum(IV) complexes that could be useful for treating cancer with fewer side effects than approved platinum-based chemotherapeutics. Full Text | PDF ADAM9; CUB domain containing protein 1 (CDCP1) doi:10.1038/scibx.2014.981 Studies in patient samples and mice suggest inhibiting ADAM9 or CDCP1 could help prevent metastasis in patients with lung cancer. Full Text | PDF Phosphoinositide 3-kinase (PI3K); cyclin dependent kinase 4 (CDK4); Bruton's tyrosine kinase (BTK) doi:10.1038/scibx.2014.982 Human tissue and cell culture studies suggest CDK4 inhibitors could help treat Imbruvica ibrutinib–resistant MCL. Full Text | PDF BRAF; epidermal growth factor receptor 3 (EGFR3; HER3; ERBB3) doi:10.1038/scibx.2014.983 Cell culture and mouse studies suggest inhibiting EGFR3 and BRAF could help treat BRAF-mutant melanomas resistant to BRAF inhibitors. Full Text | PDF Androgen receptor (AR) doi:10.1038/scibx.2014.984 Cell culture studies have identified AR-inhibiting 4-(4-phenylthiazol-2-yl) morpholine analogs that could be useful for treating drug-resistant prostate cancer. Full Text | PDF Cardiovascular disease Top Hydroxyeicosapentaenoic acid (18-HEPE) doi:10.1038/scibx.2014.985 Mouse studies suggest the eicosapentaenoic acid metabolite 18-HEPE could be useful for treating pathological cardiac remodeling. Full Text | PDF Serine/threonine kinase 3 (STK3; MST2) doi:10.1038/scibx.2014.986 Studies in human samples and mice suggest inhibiting MST2 could help treat cardiac hypertrophy. Full Text | PDF Factor Xa; thrombin (factor IIa; F2); factor IXa; factor VIIa/tissue factor complex doi:10.1038/scibx.2014.987 In vitro studies suggest a combination of aptamers that inhibit coagulation factors could help prevent thrombosis. Full Text | PDF Endocrine/metabolic disease Top Islet amyloid polypeptide (IAPP) doi:10.1038/scibx.2014.988 In vitro and mouse studies suggest enhancing β cell autophagy could help treat diabetes. Full Text | PDF Hematology Top Ret proto-oncogene (RET) doi:10.1038/scibx.2014.989 In vitro and mouse studies suggest RET agonists could improve the outcome of hematopoietic stem cell (HSC) transplants. Full Text | PDF Inflammation Top Helicobacter pylori γ-glutamyl transpeptidase (ggt); H. pylori vacuolating cytotoxin (vacA) doi:10.1038/scibx.2014.990 Mouse studies suggest ggt and vacA can help prevent allergic asthma. Full Text | PDF Neurology Top Prostaglandin D2 receptor subtype DP1 (PTGDR1; DP1); superoxide dismutase 1 (SOD1) doi:10.1038/scibx.2014.991 Cell culture and mouse studies suggest inhibiting DP1 could help treat ALS. Full Text | PDF Pulmonary disease Top Cystic fibrosis transmembrane conductance regulator (CFTR) doi:10.1038/scibx.2014.992 Cell culture studies suggest long-term studies with CFTR potentiator compounds could help assess their impact on mutant forms of the ion channel protein. Full Text | PDF Distillery: Techniques Markers Top RAC1 P29S as a marker of resistance to BRAF inhibitors in melanoma doi:10.1038/scibx.2014.1000 Mouse and cell culture studies suggest RAC1 P29S could be useful as a biomarker for resistance to BRAF inhibitors in melanoma. Full Text | PDF Assays and screens Top High-coverage, single-cell genome and exome sequencing at base-pair resolution to aid biomarker identification doi:10.1038/scibx.2014.993 A single-cell sequencing method with base-pair resolution, dubbed Nuc-seq, could be used to explore heterogeneity in cancer and other diseases to aid biomarker identification and guide therapeutic development. Full Text | PDF Disease models Top Single immunoglobulin and toll-interleukin 1 receptor domain (Sigirr; Tir8)-deficient mouse model of Campylobacter jejuni infection doi:10.1038/scibx.2014.994 Sigirr-deficient mice could serve as a model to identify new targets to treat C. jejuni infection. Full Text | PDF Drug delivery Top Targeting glioma stem-like cells (GSCs) with CpG-siRNA conjugates doi:10.1038/scibx.2014.995 Cell culture and mouse studies suggest CpG-siRNA–conjugated therapeutics could be used to target GSCs. Full Text | PDF Drug platforms Top Chimeric antigen receptor (CAR)-specific invariant NK T (iNKT) cell therapy doi:10.1038/scibx.2014.996 CAR-specific iNKT cell therapies could be designed to target various cancers without causing graft-versus-host disease (GvHD). Full Text | PDF Oncolytic virus to enhance efficacy of chimeric antigen receptor (CAR)-specific T cells doi:10.1038/scibx.2014.997 Mouse studies suggest oncolytic viruses could be used to enhance the anticancer efficacy of CAR-specific T cells. Full Text | PDF X-ray crystal structures of thiol-reactive agents in complex with Mycobacterium tuberculosis secreted antigen 85-C (fbpC; ag85C) doi:10.1038/scibx.2014.998 The crystal structures of thiol-reactive agents in complex with fbpC could aid the rational design of new therapeutic candidates to treat tuberculosis. Full Text | PDF Integrated genomic and proteomic analysis of cancer cells to prioritize the study of cancer drivers doi:10.1038/scibx.2014.999 Combined genomic and proteomic analysis of cancer cells could help prioritize which genes to study that drive the disease. Full Text | PDF Top

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