Blog of Signaling Pathways

Low-Dose Enzalutamide in Late-Elderly Patients (≥ 75 Years Old) Presenting With Metastatic Castration-Resistant Prostate Cancer.

333 views | May 19 2020

Vinh-Hung V et al. found that Low-dose enzalutamide in very old, symptomatic, poor-performance patients with metastatic disease was associated with high response rate and survival comparable to standard dose. [Read the Full Post]

Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic.

0 views | May 19 2020

Galiana I et al. supported targeted senolysis as a new therapeutic opportunity to improve outcomes in breast cancer patients [Read the Full Post]

Cerebrospinal fluid penetration of the colony-stimulating factor-1 receptor (CSF-1R) inhibitor, pexidartinib

292 views | May 18 2020

Shankarappa PS et al. found that pexidartinib was well-tolerated in NHPs, with no Grade 3 or Grade 4 toxicities. The CSF penetration of pexidartinib after single-dose oral administration to NHPs was limited. [Read the Full Post]

Discovery of suppressors of CRMP2 phosphorylation reveals compounds that mimic the behavioral effects of lithium on amphetamine-induced hyperlocomotion

455 views | May 18 2020

Zhao WN et al. not only provided insights into the neural substrates regulated by lithium, but also provided novel human neuronal assays for supporting the development of mechanism-based therapeutics for BD and related neuropsychiatric disorders. [Read the Full Post]

Chromatin mapping and single-cell immune profiling define the temporal dynamics of ibrutinib response in CLL

462 views | May 17 2020

Rendeiro AF et al. described time-dependent cellular, molecular, and regulatory effects for therapeutic inhibition of B cell receptor signaling in CLL [Read the Full Post]

Inhibition of Rb phosphorylation leads to H2S-mediated inhibition of NF-kB in acute pancreatitis and associated lung injury in mice

251 views | May 17 2020

Sundar V et al. revealed a novel link between H2S/RB/NF-κB pathways, in AP and provided insight into possible mechanism that can be targeted in prevention of inflammation to cancer development. [Read the Full Post]

Endoplasmic reticulum stress mediates resistance to BCL-2 inhibitor in uveal melanoma cells

282 views | May 16 2020

Bellini L et al. identified ABT-263 as a valid therapeutic option for patients suffering from uveal melanoma. [Read the Full Post]

Discovery of IAP-recruiting BCL-XL PROTACs as potent degraders across multiple cancer cell lines

285 views | May 16 2020

Zhang X et al. expanded the anti-tumor spectra of BCL-XL degraders and further highlight the importance of selecting suitable E3 members to achieve effective cellular activity. [Read the Full Post]

Toll-like Receptor 4 Deficiency Aggravates Airway Hyperresponsiveness and Inflammation by Impairing Neutrophil Apoptosis in a Toluene Diisocyanate-Induced Murine Asthma Model.

246 views | May 15 2020

Chen S et al. indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation. [Read the Full Post]

Combination of PARP inhibitor olaparib, and PD-L1 inhibitor durvalumab, in recurrent ovarian cancer: a proof-of-concept phase 2 study.

335 views | May 15 2020

Lampert EJ et al. found that he PARPi and anti-PD-L1 combination showed modest clinical activity in recurrent ovarian cancer. Their correlative study results suggested immunomodulatory effects by olaparib/durvalumab in patients and indicate that VEGF/VEGFR pathway blockade would be necessary for improved efficacy of the combination [Read the Full Post]

Glucagon-like peptide 1 reverses myocardial hypertrophy through cAMP/PKA/RhoA/ROCK2 signaling.

867 views | May 14 2020

Fan S et al. suggested that GLP-1 might reverse myocardial hypertrophy through the PKA/RhoA/ROCK2 signaling pathway. [Read the Full Post]

"Direct to Drug" screening as a precision medicine tool in multiple myeloma.

233 views | May 14 2020

Bonolo de Campos C et al. found that this "direct to drug" screening resource, paired with functional genomics, had the potential to successfully direct appropriate individualized therapeutic approaches in MM and to enrich clinical trials for likely responders. [Read the Full Post]

Functional evaluation of five BRCA2 unclassified variants identified in a Sri Lankan cohort with inherited cancer syndromes using a mouse embryonic stem cell-based assay

319 views | May 13 2020

Sirisena N et al. highlighted the value of mouse embryonic stem cell-based assays for determining the functional significance of variants of unknown clinical significance and provide valuable information regarding risk estimation and genetic counseling of families carrying these BRCA2 variants. [Read the Full Post]

Inhibition of the erythropoietin-producing receptor EPHB4 antagonizes androgen receptor overexpression and reduces enzalutamide resistance

0 views | May 13 2020

Li C et al. provided critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy. [Read the Full Post]

The Rho-associated kinase inhibitor fasudil can replace Y-27632 for use in human pluripotent stem cell research

1234 views | May 12 2020

So S et al. suggested that fasudil can replace Y-27632 for use in stem research. [Read the Full Post]

Dual targeting of BCL2 and MCL1 rescues myeloma cells resistant to BCL2 and MCL1 inhibitors associated with the formation of BAX/BAK hetero-complexes

205 views | May 12 2020

Seiller C et al. found that BCLXL remains a major resistant factor of cell death induced by this combination. [Read the Full Post]

Kallikrein-related peptidase (KLK10) cessation blunts colorectal cancer cell growth and glucose metabolism by regulating the PI3K/Akt/mTOR pathway

310 views | May 11 2020

Wei H et al. suggested that KLK10 silencing may attenuate the progression of CRC by inhibiting cell growth and glycolysis via the PI3K/AKT/mTOR signaling, supporting a potential and promising target for CRC therapy. [Read the Full Post]

Attenuation of canonical NF-κB signaling maintains function and stability of human Treg

807 views | May 11 2020

Ziegler LS et al. provided first insights into the role of NF-κB signaling in human Treg. [Read the Full Post]

Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1alpha

500 views | May 10 2020

Koh MY et al. concluded that PX-478 inhibits HIF-1alpha at multiple levels that together or individually may contribute to its antitumor activity against HIF-1alpha-expressing tumors. [Read the Full Post]

anlotinib alters tumor immune microenvironment by downregulating PD-L1 expression on vascular endothelial cells

363 views | May 10 2020

Liu S et al. demonstrated that PD-L1 high expression on VECs inhibits the infiltration of CD8+ T cells, whereas promotes the aggregation of FoxP3+ T cells into tumor tissues, thus becoming an "immunosuppressive barrier". Anlotinib can ameliorate the immuno-microenvironment by downregulating PD-L1 expression on VECs to inhibit tumor growth. [Read the Full Post]