Category
- PI3K/Akt/mTOR
- Epigenetics
- Methylation
- Immunology & Inflammation
- Protein Tyrosine Kinase
- Angiogenesis
- Apoptosis
- Autophagy
- ER stress & UPR
- JAK/STAT
- MAPK
- Cytoskeletal Signaling
- Cell Cycle
- TGF-beta/Smad
- DNA Damage
- Stem Cells & Wnt
- Ubiquitin
- Neuronal Signaling
- NF-κB
- GPCR & G Protein
- Endocrinology & Hormones
- Transmembrane Transporters
- Metabolism
- Proteases
- Microbiology
- Others
Archives
ALK
The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models
39 views | Nov 02 2019
Zhang S et al. provided the molecular basis for the promising activity being observed in ALK+, crizotinib-resistant patients with NSCLC being treated with brigatinib in clinical trials. [Read the Full Post]
Phase I Study of Ceritinib (LDK378) in Japanese Patients with Advanced, Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer or Other Tumors
40 views | Oct 16 2019
Nishio M et al. indicated that ceritinib maximum-tolerated dose was 750 mg once daily in Japanese patients. Antitumor activity was observed irrespective of prior ALKi treatment history. Dose expansion, examining the activity of ceritinib in alectinib-resistant patients, is ongoing. [Read the Full Post]
Brief Report: Rapid Acquisition of Alectinib Resistance in ALK-positive Lung Cancer with High Tumor Mutation Burden
72 views | Aug 16 2019
Makimoto G et al. found that high TMB and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. [Read the Full Post]
PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations
115 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]
Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase
204 views | Jun 12 2019
Huang WS et al. showed that brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial. [Read the Full Post]
NK92-CD16 cells are cytotoxic to non-small cell lung cancer cell lines that have acquired resistance to tyrosine kinase inhibitors
193 views | Jun 08 2019
Park HR et al. suggested that combinational treatment with NK cell-based immunotherapy and cetuximab may be promising for patients with TKI-resistant NSCLC. [Read the Full Post]
Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial
166 views | May 07 2019
Shaw AT et al. indicated lorlatinib might be an effective therapeutic strategy for patients with ALK-positive NSCLC who have become resistant to currently available TKIs, including second-generation ALK TKIs, and is being investigated in a phase 3 randomised controlled trial comparing lorlatinib to crizotinib (ClinicalTrials.gov, NCT03052608). [Read the Full Post]
Favorable predictors for survival in advanced ALK-positive non-small cell lung cancer patients beyond crizotinib resistance
191 views | Apr 24 2019
Xu H et al. found that long PFS with crizotinib (≥10.4 months), intracranial progression, and use of next-generation ALK inhibitors might be favorable predictors for OS in advanced ALK-positive NSCLC patients. [Read the Full Post]
No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone
0 views | Nov 04 2018
Peterse EF et al. indicated that the IGF pathway is not essential for chondrosarcoma growth, migration or chemoresistance. Furthermore, IGF1R is only minimally expressed in chondrosarcoma primary tumours. Therefore, the IGF pathway is not expected to be an effective therapeutic target for chondrosarcoma of bone. [Read the Full Post]
Identification of different ALK mutations in a pair of neuroblastoma cell lines established at diagnosis and relapse
657 views | May 02 2018
Chen L et al. showed that use both Sanger and targeted deep sequencing, this study describes the identification of distinct ALK mutations in these paired cell lines, including the rare R1275L mutation, which has not previously been reported in a neuroblastoma cell line. Analysis of the sensitivity of NBLW and NBLW-R cells to a panel of ALK inhibitors (TAE-684, Crizotinib, Alectinib and Lorlatinib) revealed differences between the paired cell lines, and overall NBLW-R cells with the F1174L mutation were more resistant to ALK inhibitor induced apoptosis compared with NBLW cells. This pair of cell lines represents a valuable pre-clinical model of clonal evolution of ALK mutations associated with neuroblastoma progression. [Read the Full Post]
