Blog of Signaling Pathways

Treatment Patterns in Patients with Chronic-Phase Chronic Myeloid Leukaemia in Routine Clinical Practice: the SIMPLICITY Italian Population

1398 views | Aug 10 2019

Abruzzese E et al. provided valuable insights into management and treatment patterns in Italian patients with CML within routine clinical practice. [Read the Full Post]

Inhibition of the amino-acid transporter LAT1 demonstrates anti-neoplastic activity in medulloblastoma

482 views | Aug 10 2019

Cormerais Y et al. demonstrated that a long-term treatment with JPH203 does not lead to resistance in MB cells. Therefore, this study suggests that targeting LAT1 with JPH203 is a promising therapeutic approach for MB treatment. [Read the Full Post]

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

534 views | Aug 09 2019

Chen YN et al. demonstrated that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers. [Read the Full Post]

Irinotecan monotherapy as third-line or later treatment in advanced gastric cancer

496 views | Aug 09 2019

Makiyama A et al. showed that Irinotecan monotherapy was relatively safely performed as salvage-line treatment for AGC in Japanese clinical practice. Careful patient selection and intensive modification of the dose of irinotecan might possibly be associated with favorable survival. [Read the Full Post]

Protection of Mcc950 against high-glucose-induced human retinal endothelial cell dysfunction

451 views | Aug 08 2019

Zhang Y et al. showed that Mcc950 inhibited HREC dysfunction under high-glucose conditions and this research may offer insight for future pharmaceutical approaches for treating DR. [Read the Full Post]

Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis

975 views | Aug 07 2019

Verstovsek S et al. indicated that INCB018424 was associated with marked and durable clinical benefits in patients with myelofibrosis for whom no approved therapies existed. [Read the Full Post]

Targeting autophagy potentiates the anti-tumor effect of PARP inhibitor in pediatric chronic myeloid leukemia

575 views | Aug 07 2019

Liu Y et al. demonstrated that autophagy played a cyto-protective role in talazoparib-treated pediatric CML and co-treatment with talazoparib and autophagy inhibitor could induce synergetic anti-tumor effect, providing novel insights for pediatric CML treatment. [Read the Full Post]

Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death

401 views | Aug 06 2019

Kwon MY et al. showed that hemin and CORM accelerate the HO-1 expression in the presence of Erastin and increase membranous lipid peroxidation. Thus, HO-1 is an essential enzyme for iron-dependent lipid peroxidation during ferroptotic cell death. [Read the Full Post]

RSL3 and Erastin differentially regulate redox signaling to promote Smac mimetic-induced cell death

0 views | Aug 06 2019

Dächert J et al. showed that RSL3/BV6 and Erastin/BV6 differentially regulate redox signaling and cell death in ALL cells. While RSL3/BV6 cotreatment induces ferroptotic cell death, Erastin/BV6 stimulates oxidative cell death independently of iron. These findings have important implications for the therapeutic targeting of redox signaling to enhance Smac mimetic-induced cell death in ALL. [Read the Full Post]

Supramolecular Nanorods of (N-Methylpyridyl) Porphyrin With Captisol: Effective Photosensitizer for Anti-bacterial and Anti-tumor Activitie

582 views | Aug 05 2019

Khurana R et al. indicatted that all these synergistic effects of supramolecular nanorods of Captisol-TMPyP complex make the system an effective photosensitizer and a superior antibacterial and antitumor agent. [Read the Full Post]

PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations

1072 views | Aug 05 2019

Zou HY et al. indicated that PF-06463922 has potential for treating ROS1 fusion-positive cancers, including those requiring agents with CNS-penetrating properties, as well as for overcoming crizotinib resistance driven by ROS1 mutation. [Read the Full Post]

Human primary liver cancer-derived organoid cultures for disease modeling and drug screening

595 views | Aug 04 2019

Broutier L et al. demonstrated the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease. [Read the Full Post]

Phase Ib study of the combination of pexidartinib (PLX3397), a CSF-1R inhibitor, and paclitaxel in patients with advanced solid tumors

431 views | Aug 03 2019

Wesolowski R et al. showed the combination of pexidartinib and paclitaxel was generally well tolerated. RP2D for pexidartinib was 1600 mg/day. Pexidartinib blocked CSF-1R signaling, indicating potential for mitigating macrophage tumor infiltration. [Read the Full Post]

Conversion of Terminally Committed Hepatocytes to Culturable Bipotent Progenitor Cells with Regenerative Capacity

597 views | Aug 03 2019

Katsuda T et al. reported that a cocktail of small molecules, Y-27632, A-83-01, and CHIR99021, can convert rat and mouse MHs in vitro into proliferative bipotent cells, which we term chemically induced liver progenitors (CLiPs). CLiPs can differentiate into both MHs and biliary epithelial cells that can form functional ductal structures. CLiPs in long-term culture did not lose their proliferative capacity or their hepatic differentiation ability, and rat CLiPs were shown to extensively repopulate chronically injured liver tissue. Thus, our study advances the goals of liver regenerative medicine. [Read the Full Post]

Bafilomycin A1 triggers proliferative potential of senescent cancer cells in vitro and in NOD/SCID mice

523 views | Aug 01 2019

Was H et al. suggested that senescent cancer cells that appear during therapy, can be considered as dormant cells that contribute to cancer re-growth, when chemotherapeutic treatment is stopped. These data unveil new mechanisms of TIS-related cancer maintenance and re-population, triggered by a single pulse of BAF A1 treatment. [Read the Full Post]

A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2- Metastatic Breast Cancer

0 views | Jul 31 2019

Mayer IA et al. showed that alpelisib's maximum-tolerated dose (MTD) in combination with letrozole was 300 mg/d. Common drug-related adverse events included hyperglycemia, nausea, fatigue, diarrhea, and rash with dose-limiting toxicity occurring at 350 mg/d of alpelisib. The clinical benefit rate (lack of progression ≥6 months) was 35% (44% in patients with PIK3CA-mutated and 20% in PIK3CA wild-type tumors; 95% CI, 17%-56%), including five objective responses. Of eight patients remaining on treatment ≥12 months, six had tumors with a PIK3CA mutation. Among evaluable tumors, those with FGFR1/2 amplification and KRAS and TP53 mutations did not derive clinical benefit. Overexpression of FGFR1 in ER+/PIK3CA mutant breast cancer cells attenuated the response to alpelisib in vitro CONCLUSIONS: The combination of letrozole and alpelisib was safe, with reversible toxicities. Clinical activity was observed independently of PIK3CA mutation status, although clinical benefit was seen in a higher proportion of patients with PIK3CA-mutated tumors. Phase II and III trials of alpelisib and endocrine therapy in patients with ER+ breast cancer are ongoing. [Read the Full Post]

The 5-hydrazino-3-methylisothiazole-4-carboxylic acid, its new 5-substituted derivatives and their antiproliferative activity

471 views | Jul 29 2019

Jęśkowiak I et al. showed in the conducted studies, their activity against breast adenocarcinoma MCF-7 and normal non-tumorigenic epithelial cell line derived from mammary gland MCF-10A was substantially lower. The result of this work is claimed Polish patent application. [Read the Full Post]

Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer

446 views | Jul 29 2019

Gross MI et al. provided a strong rationale for the clinical investigation of CB-839 as a targeted therapeutic in patients with TNBC and other glutamine-dependent tumors. [Read the Full Post]

Kinetic Tuning of HDAC Inhibitors Affords Potent Inducers of Progranulin Expression

0 views | Jul 27 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]

Reversal of sorafenib resistance in hepatocellular carcinoma: epigenetically regulated disruption of 14-3-3η/hypoxia-inducible factor-1α

350 views | Jul 26 2019

Qiu Y et al. indicated that miR-16/14-3-3η is involved in sorafenib resistance in HCC and that these two factors could be potential therapeutic targets and biomarkers for predicting the response to sorafenib treatment. [Read the Full Post]