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Blog of Signaling Pathways

The phosphoinositide 3'-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia

1 views | Sep 16 2019

Hoellenriegel J et al. provided an explanation for the clinical activity of CAL-101, and a roadmap for future therapeutic development. [Read the Full Post]

GS-1101: a delta-specific PI3K inhibitor in chronic lymphocytic leukemia

2 views | Sep 16 2019

Macias-Perez IM et al. indicated this article will review new insights into the pathophysiology of CLL, the preclinical rationale of a PI3Kδ inhibitor in CLL, and the clinical evidence supporting this first-in-class therapeutic target for CLL patients. [Read the Full Post]

Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth

1 views | Sep 15 2019

Yakes FM et al. suggested that cabozantinib is a promising agent for inhibiting tumor angiogenesis and metastasis in cancers with dysregulated MET and VEGFR signaling. [Read the Full Post]

Effective combinatorial immunotherapy for castration-resistant prostate cancer

0 views | Sep 15 2019

Lu X et al. illuminated a clinical path hypothesis for combining immune checkpoint blockade with MDSC-targeted therapies in the treatment of mCRPC. [Read the Full Post]

LBH589 Inhibits Glioblastoma Growth and Angiogenesis Through Suppression of HIF-1α Expression

1 views | Sep 14 2019

Yao ZG et al. supports the role of HDAC inhibitors as a therapeutic strategy to target tumor angiogenesis. [Read the Full Post]

Axl Blockade by BGB324 Inhibits BCR-ABL Tyrosine Kinase Inhibitor-Sensitive and -Resistant Chronic Myeloid Leukemia

1 views | Sep 14 2019

Erdmann R et al. showed that Axl inhibition has therapeutic potential in BCR-ABL TKI-sensitive as well as -resistant CML and support the need for clinical trials. [Read the Full Post]

Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation

1 views | Sep 12 2019

Fokas E et al. support ATR inhibition as a promising new approach to improve the therapeutic ration of radiochemotherapy for patients with PDAC. [Read the Full Post]

Panobinostat for the Treatment of Multiple Myeloma

1 views | Sep 12 2019

Laubach JP et al. indicated The review focuses on panobinostat and its mechanism of action, pharmacokinetics, and clinical data in the treatment of relapsed or relapsed and refractory multiple myeloma. [Read the Full Post]

Autophagy inhibitor 3-methyladenine protects against endothelial cell barrier dysfunction in acute lung injury

1 views | Sep 11 2019

Slavin SA et al. indicated these data imply a role of autophagy in lung vascular injury and reveal the protective and therapeutic utility of 3-MA against ALI. [Read the Full Post]

Synthesis and screening of 3-MA derivatives for autophagy inhibitors

2 views | Sep 11 2019

Wu Y et al. demonstrated that chemical modification of an existing autophagy inhibitor is an effective method to generate improved autophagy inhibitors. [Read the Full Post]

Kinetic Tuning of HDAC Inhibitors Affords Potent Inducers of Progranulin Expression

24 views | Sep 09 2019

Moreno-Yruela C et al. demonstrated induction of PGRN expression by fast-on/fast-off, highly potent, macrocyclic HDAC inhibitors with ethyl ketone or ethyl ester Zn2+ binding groups. [Read the Full Post]

SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells

21 views | Sep 09 2019

Sun QY et al. revealed an unappreciated role of SOX7 in regulation of cellular apoptosis through control of MAPK/ERK-BIM signaling. [Read the Full Post]

Activation of Wnt signaling promotes olaparib resistant ovarian cancer

14 views | Sep 08 2019

Yamamoto TM et al. demonstrated that Wnt signaling can mediate PARPi resistance in HGSOC and provides a clinical rationale for combining PARP and Wnt inhibitors. [Read the Full Post]

Rucaparib: the past, present, and future of a newly approved PARP inhibitor for ovarian cancer

13 views | Sep 08 2019

Dockery LE et al. indicated this article reviews the mechanisms of action, safety, approval, and indications for use of the PARP inhibitor rucaparib as well as future trials and use of rucaparib's companion diagnostic test. [Read the Full Post]

BYL719, a new α-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma

33 views | Sep 07 2019

Gobin B et al. indicated the present work shows that BYL719 is a promising drug in either a single or multidrug approach to curing bone sarcoma. [Read the Full Post]

Bafilomycin A1 disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion

16 views | Sep 07 2019

Mauvezin C et al. identified the ER-calcium ATPase Ca-P60A/dSERCA as a novel target of bafilomycin A1. Autophagosome-lysosome fusion was defective in Ca-P60A/dSERCA-depleted cells, and bafilomycin A1 induced a significant increase in cytosolic calcium concentration and disrupted Ca-P60A/SERCA-mediated fusion. Thus, bafilomycin A1 disrupts autophagic flux by independently inhibiting V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion. [Read the Full Post]

Fenretinide via NOXA induction, enhanced activity of the BCL-2 inhibitor venetoclax in high BCL-2-expressing neuroblastoma preclinical models

2 views | Sep 06 2019

Reynolds CP et al. found that fenretinide + ventoclax is a synergistic combination that warrants clinical testing in high BCL-2 expressing neuroblastoma. [Read the Full Post]

An in vitro assay for biomarker discovery and dose prediction applied to ibrutinib plus venetoclax treatment of CLL

0 views | Sep 06 2019

Skånland SS et al. suggested that phospho flow should be considered as a novel approach for dose and synergy prediction in a precision medicine setting for CLL. [Read the Full Post]

Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV-1 study

7 views | Sep 05 2019

Yurdaydin C et al. showed the cytochrome P450 3A4 inhibitor, RTV, allows a lower LNF dose to be used while achieving higher levels of postabsorption LNF, yielding better antiviral responses and tolerability. In addition, combining LNF with PEG-IFNα achieved more substantial and rapid HDV-RNA reduction, compared to historical responses with PEG-IFNα alone. Twelve weeks of LNF can result in posttreatment HDV-RNA negativity in some patients, which we speculate results from restoring favorable immune responses. These results support further development of LNF with RTV boosting and exploration of the combination of LNF with PEG-IFN. [Read the Full Post]

Activity of BET-proteolysis targeting chimeric (PROTAC) compounds in triple negative breast cancer

5 views | Sep 05 2019

Noblejas-López MDM et al. provided options for further clinical development of these agents in TNBC. [Read the Full Post]