A5114209656- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Cancer therapeutics and mechanisms
- Lung Cancer Treatments and Mutations
- Cancer Mechanisms and Therapy
- PI3K/AKT/mTOR signaling in cancer
Frederick National Laboratory for Cancer Research
2024-2025
National Institutes of Health
2024-2025
National Cancer Institute
2023-2025
Center for Cancer Research
2024-2025
The worldwide annual frequency and lethality of head neck squamous cell carcinoma (HNSCC) is not improving, thus, new therapeutic approaches are needed. Approximately 70% HNSCC cases have either amplification or overexpression MAP3K13 , which encodes the kinase LZK. Here, we found that LZK a target in small-molecule inhibition its catalytic function decreased viability cells with amplified . Inhibition suppressed tumor growth -amplified xenografts derived from patients. stabilized...
PIM kinases have important pro-tumorigenic roles and mediate several oncogenic traits, including cell proliferation, survival, chemotherapeutic resistance. As a result, multiple inhibitors been pursued as investigational new drugs in cancer; however, response to solid tumors has fallen short of expectations. We found that inhibition kinase activity stabilizes protein levels all three isoforms (PIM1/2/3), this can promote resistance chemotherapy. To overcome effect, we designed proteolysis...
Abstract The worldwide frequency of head and neck squamous cell carcinoma (HNSCC) is approximately 800,000 new cases, with 430,000 deaths annually. We determined that LZK (encoded by MAP3K13 ) a therapeutic target in HNSCC showed inhibition small molecule inhibitors decreases the viability cells amplified . A drug-resistant mutant blocks due to inhibition, indicating on-target activity two separate molecules. Inhibition catalytic suppressed tumor growth PDX models found kinase stabilized...