Blog of Signaling Pathways

PK-PD modeling of combination efficacy effect from administration of the MEK inhibitor GDC-0973 and PI3K inhibitor GDC-0941 in A2058 xenografts

368 views | Nov 20 2019

Choo EF et al. suggested that, based on minimal data, it is possible to predict the effects of various combinations preclinically and also assess the potential clinical efficacy of combinations using human pharmacokinetic inputs. [Read the Full Post]

A Genome-Wide CRISPR Screen Identifies Genes Critical for Resistance to FLT3 Inhibitor AC220

0 views | Nov 19 2019

Hou P et al. identified novel genes whose loss of function conferred resistance to a selective FLT3 inhibitor, providing new insight into signaling pathways that contribute to acquired resistance in AML. [Read the Full Post]

Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer

473 views | Nov 18 2019

McGivern N et al. provided a preclinical rationale for the combination of SRC and MEK inhibitors in the treatment of ovarian cancer, and also highlights the need for biomarker driven patient selection for clinical trials. [Read the Full Post]

Differential cellular responses induced by dorsomorphin and LDN-193189 in chemotherapy-sensitive and chemotherapy-resistant human epithelial ovarian cancer cells

451 views | Nov 18 2019

Ali JL et al. showed that DM and LDN possess drug characteristics suitable for adjuvant agents used to treat chemotherapy-sensitive and -resistant EOC. [Read the Full Post]

ICG-001 suppresses growth of gastric cancer cells and reduces chemoresistance of cancer stem cell-like population

0 views | Nov 17 2019

Liu Y et al. suggested that ICG-001 suppresses GC cell line growth, metastasis and reduces its stem cell-like properties and chemoresistance, indicating that ICG-001 is a potentially useful small molecule therapeutic for GC. [Read the Full Post]

PTTG1 Levels Are Predictive of Saracatinib Sensitivity in Ovarian Cancer Cell Lines

484 views | Nov 17 2019

Nakachi I et al. indicated PTTG1 may be a valuable biomarker in ovarian cancer to predict sensitivity to saracatinib, and could form the basis of a targeted prospective saracatinib trial for ovarian cancer. [Read the Full Post]

The successful use of pembrolizumab in a renal transplant recipient with metastatic melanoma

423 views | Nov 16 2019

Hanna DL et al. reported a case in which a renal transplant recipient with metastatic melanoma had an excellent response to treatment with second line programmed cell death protein 1 (PD-1) inhibitor therapy, pembrolizumab. [Read the Full Post]

Growth Arrest Specific Protein (Gas)-6/AXL Signaling Induces Preeclampsia (PE) in Rats

455 views | Nov 16 2019

Hirschi KM et al.provided insight into pathways associated with PE that could be useful in the clarification of potential therapeutic approaches. [Read the Full Post]

NU7441 Enhances the Radiosensitivity of Liver Cancer Cells

598 views | Nov 15 2019

Yang C et al. showed that NU7441 inhibited the growth of liver cancer cells, enhanced the radiosensitization of these cancer cells by interfering with the DNA repair and cell cycle checkpoint. These data implicate NU7441 as a potential radiotherapy sensitizer for the treatment of liver cancer. [Read the Full Post]

Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks

0 views | Nov 15 2019

Zhou T et al. indicated this chromosomal hypersensitivity, as well as a small but reproducible enhancement of calicheamicin cytotoxicity following siRNA-mediated TDP1 knockdown, suggests a role for TDP1 in repair of 3'-PG double-strand breaks in vivo. [Read the Full Post]

LY2109761 enhances cisplatin antitumor activity in ovarian cancer cells

588 views | Nov 14 2019

Gao Y et al. showed that chemotherapeutic approaches using LY2109761 might enhance the treatment benefit of the cisplatin in the treatment of ovarian cancer patients. [Read the Full Post]

BX-795 inhibits HSV-1 and HSV-2 replication by blocking the JNK/p38 pathways without interfering with PDK1 activity in host cells

759 views | Nov 14 2019

Su AR et al. identified the anti-HSV activity of BX-795 and its targeting of the JNK/p38 MAP kinase pathways in host cells. [Read the Full Post]

Epigenetic Profiling Identifies LIF as a Super-enhancer-Controlled Regulator of Stem Cell-like Properties in Osteosarcoma

692 views | Nov 12 2019

Lu B et al. revealed osteosarcoma SE profiles and uncovers a distinct tumor-stemness epigenetic regulatory mechanism in which an osteosarcoma-specific SE-mediated factor, LIF, promotes osteosarcoma stemness gene activation via NOTCH1 signaling pathway. [Read the Full Post]

Corrector VX-809 promotes interactions between cytoplasmic loop one and the first nucleotide-binding domain of CFTR

414 views | Nov 12 2019

Loo TW et al. suggested that the mechanism by which VX-809 promotes maturation and stability of CFTR is by promoting CL1/NBD1 interactions. [Read the Full Post]

The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress

0 views | Nov 11 2019

Ren Y et al. showed the Sirt1 activator may therefore be prove to be a potent therapeutic agent for the treatment of fibrotic kidney disease. [Read the Full Post]

Effects of pentoxifylline and H-89 on epileptogenic activity of bucladesine in pentylenetetrazol-treated mice

515 views | Nov 11 2019

Hosseini-Zare MS et al. showed that seizure activities were affected by pentoxifylline, H-89 and bucladesine via interactions with intracellular cAMP and cGMP signaling pathways, cyclic nucleotide-dependent protein kinases, and related neurotransmitters. [Read the Full Post]

Treatment with XAV-939 prevents in vitro calcification of human valvular interstitial cells

501 views | Nov 10 2019

Dittfeld C et al. indicated that XAV-939 was therefore able to prevent calcification of human VIC cultures, and XAV-939 treatment was accompanied by upregulation of active non-phospho-β-catenin. Although XAV-939 does not downregulate active β-catenin, treatment with XAV-939 results in Sox9 upregulation that may prevent the calcification process. [Read the Full Post]

The novel inhibitor PRI-724 for Wnt/β-catenin/CBP signaling ameliorates bleomycin-induced pulmonary fibrosis in mice

1387 views | Nov 10 2019

Okazaki H et al. suggested that the β-catenin/CBP inhibitor PRI-724 is a potent antifibrotic agent that acts by modulating the activity of macrophages in the lungs. [Read the Full Post]

Dual mTORC1/2 inhibition by INK-128 results in antitumor activity in preclinical models of osteosarcoma

0 views | Nov 08 2019

Jiang H et al. showed that INK-128 exerts potent anti-OS activity in vitro and in vivo. INK-128 might be further investigated as a novel anti-OS agent. [Read the Full Post]

Pan-mTOR inhibitor MLN0128 is effective against intrahepatic cholangiocarcinoma in mice

299 views | Nov 08 2019

Zhang S et al. suggested that mTOR kinase inhibitors may be beneficial for the treatment of ICC, even in tumors that are resistant to standard of care chemotherapeutics, such as gemcitabine/oxaliplatin-based regimens, especially in the subset of tumors exhibiting activated AKT/mTOR cascade. Lay summary: We established a novel mouse model of intrahepatic cholangiocarcinoma (ICC). Using this new preclinical model, we evaluated the therapeutic potential of mTOR inhibitor MLN0128 vs. gemcitabine/oxaliplatin (the standard chemotherapy for ICC treatment). Our study shows the anti-neoplastic potential of MLN0128, suggesting that it may be superior to gemcitabine/oxaliplatin-based chemotherapy for the treatment of ICC, especially in the tumors exhibiting activated AKT/mTOR cascade. [Read the Full Post]