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Blog of Signaling Pathways

AZD1208, a Pan-Pim Kinase Inhibitor, Has Anti-Growth Effect on 93T449 Human Liposarcoma Cells via Control of the Expression and Phosphorylation of Pim-3, mTOR, 4EBP-1, S6, STAT-3 and AMPK

97 views | Feb 17 2020

Yadav AK et al. demonstrated that AZD1208 inhibits growth of liposarcoma cells and that this activity is mediated through Pim-3 kinase, STAT-3, mTOR, S6 and AMPK expression and phosphorylation pathways. [Read the Full Post]

Targeting KRAS Mutant Cancers With a Covalent G12C-Specific Inhibitor

80 views | Feb 17 2020

Matthew R Janes et al. provided in vivo evidence that mutant KRAS can be selectively targeted and reveals ARS-1620 as representing a new generation of KRASG12C-specific inhibitors with promising therapeutic potential. [Read the Full Post]

Administration of Lapatinib with Food Increases Its Plasma Concentration in Chinese Patients with Metastatic Breast Cancer: A Prospective Phase II Study

158 views | Feb 16 2020

Xu F et al. showed that receiving lapatinib with food can increase its plasma concentration with no significantly increased drug-related toxicity. We suggest that a larger-sample-size clinical trial is needed to fully understand the effect of administration of lapatinib with food. [Read the Full Post]

Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery

0 views | Feb 16 2020

Colclough N et al. demonstrated how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders. [Read the Full Post]

Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition

106 views | Feb 14 2020

Hong AL et al. identified a synthetic lethal relationship between SMARCB1-deficient cancers and reliance on the UPS which provides the foundation for a mechanism-informed clinical trial with proteasome inhibitors. [Read the Full Post]

Multiple myeloma with 1q21 amplification is highly sensitive to MCL-1 targeting

73 views | Feb 14 2020

Slomp A et al. indicated that amplification of 1q21 identifies an MM subset highly sensitive to MCL-1 inhibitor treatment and can be used as a predictive marker to guide selection of therapy. [Read the Full Post]

RIP3 inhibition protects locomotion function through ameliorating mitochondrial antioxidative capacity after spinal cord injury

0 views | Feb 13 2020

Wang Y et al. suggested improving antioxidative capacity as a potential multifunctional treatment after SCI and the broader possibility of targeting RIP3 activity as a therapeutic window for spinal neuroprotective intervention. [Read the Full Post]

L-Cystathionine Protects against Homocysteine-Induced Mitochondria-Dependent Apoptosis of Vascular Endothelial Cells

64 views | Feb 13 2020

Wang X et al. indicated that L-cystathionine could protect against homocysteine-induced mitochondria-dependent apoptosis of HUVECs. [Read the Full Post]

AKT Antagonist AZD5363 Influences Estrogen Receptor Function in Endocrine-Resistant Breast Cancer and Synergizes with Fulvestrant (ICI182780) In Vivo

113 views | Feb 12 2020

Ribas R et al. supported the combination of AZD5363 with fulvestrant as a potential therapy for breast cancer that is sensitive or resistant to E-deprivation or tamoxifen and that activated AKT is a determinant of response, supporting the need for clinical evaluation. [Read the Full Post]

The JAK2 inhibitor AZD1480 inhibits hepatitis A virus replication in Huh7 cells

194 views | Feb 12 2020

Jiang X et al. proposed that AZD1480 can inhibit HAV IRES activity and HAV replication through the inhibition of the La protein. [Read the Full Post]

MiR-509-3 augments the synthetic lethality of PARPi by regulating HR repair in PDX model of HGSOC

103 views | Feb 11 2020

Sun C found that MiR-509-3 can sensitize ovarian cancer cells to Olaparib by impeding HR, which makes it a potential target in PARPi synergistic treatment. [Read the Full Post]

Venetoclax in acute myeloid leukemia - current and future directions

77 views | Feb 11 2020

Lachowiez C et al. provided biological and clinical rationale for current venetoclax based treatments in AML, addresses common adverse events encountered with venetoclax based therapy, and explores emerging clinical data regarding combinations of novel targeted therapeutics used in conjunction with venetoclax for the treatment of AML. [Read the Full Post]

Rho-kinase ROCK inhibitors reduce oligomeric tau protein

190 views | Feb 10 2020

Hamano T et al. suggested that ROCK inhibitors represent a viable therapeutic route to reduce the pathogenic forms of tau protein in tauopathies, including Alzheimer's disease. [Read the Full Post]

Synergistic lethality between PARP-trapping and alantolactone-induced oxidative DNA damage in homologous recombination-proficient cancer cells

116 views | Feb 10 2020

Wang H found that PARP trapping combined with specific pro-oxidative agents may provide safe and effective ways to broaden the therapeutic potential of PARP inhibitors. [Read the Full Post]

Skin toxicity and efficacy of sunitinib and sorafenib in metastatic renal cell carcinoma: a national registry-based study

85 views | Feb 09 2020

Poprach A et al. found that the presence of skin toxicity is associated with improved OS and PFS in patients with mRCC treated with sunitinib. [Read the Full Post]

The histone deacetylase inhibitor romidepsin spares normal tissues while acting as an effective radiosensitiser in bladder tumours in vivo

147 views | Feb 09 2020

Paillas S et al. demonstrated that romidepsin is an effective radiosensitiser in vitro and in vivo and does not increase the acute and late toxicity after ionising radiation. [Read the Full Post]

The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity

85 views | Feb 08 2020

Timm KN et al. introduced different agents known to activate AMPK (metformin, statins, resveratrol, thiazolidinediones, AICAR, specific AMPK activators) as well as exercise and dietary restriction, and discussed the existing evidence for their potential role in cardioprotection from doxorubicin cardiotoxicity. [Read the Full Post]

Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive Her2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

65 views | Feb 08 2020

Demir A et al. demonstrated that the efficacy of palbociclib among heavily treated hormone receptor-positive/HER2-negative advanced BC patients was acceptable clinical benefit, and it was generally well tolerated among this population. [Read the Full Post]

Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib

241 views | Feb 07 2020

Casavecchia G et al. reported and discussed most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. [Read the Full Post]

Role of H3K18ac-regulated nucleotide excision repair-related genes in arsenic-induced DNA damage and repair of HaCaT cells

139 views | Feb 07 2020

Zhang AL et al. provided new ideas for understanding the molecular mechanisms underlying arsenic-induced skin damage. [Read the Full Post]