Ubiquitin specific protease 7 (USP7) is a deubiquitinase, an enzyme that removes ubiquitin a 76 amino acid protein that is added onto lysines in the target protein. Proteins that are mono, or poly (up to 10 residues), ubiquitinated are taken to the proteasome for destruction. Continue reading
Tag Archives: Mdm2
MDM2 and MDMX inhibitor restores p53 functioning in cancers with wild-type p53
P53 is a tumor suppressor gene that pauses cell division to allow for repair of gene damage, and triggers apoptosis if the damage is not reparable. Loss of p53 is a critical step in the evolution of cancer. Most frequently, p53 is mutated at its DNA binding domain; since p53 is a transcription factor, a diminished ability to bind to DNA significantly disrupts its functioning. Continue reading
Cancer vaccine + PD-L1 inhibitor, avelumab (Bavencio), for breast cancer
PD-L1 inhibitor, avelumab (Bavencio – Merck KGaA and Pfizer) will be combined with EpiThany’s EP-101 STEMVAC in patients with breast cancer. Avelumab was recently approved for Merckel cell carcinoma. STEMVAC is a poly-epitope DNA plasmid vaccine in the midst of a phase 1 trial of the vaccine in patients with Stage III or IV patients with breast cancer who have no evidence of disease (NED) or stable bone disease, only. The goals of the study are: Continue reading
Hyperprogression on Checkpoint Inhibition Immunotherapy
Results with checkpoint inhibitors nivolumab (PD-1, Opdivo), pembrolizumab (PD-1, Keytruda), and atezolizumab (PD-L1, Tecentriq) are impressive. Some patients have experienced incredible and prolonged responses. These drugs are truly modern medical breakthroughs.
Continue reading
CDKN2A Mutation Shortens Survival in Melanoma Patients
Individuals that carry mutations to the CDKN2A tumor suppressor gene have 65-fold increased risk of developing melanoma and a lifetime penetrance of melanoma of 60-90%. In a new study by researchers from the Karolinska University Hospital in Sweden, individuals who had inherited CDKN2A mutations were on average 10 years younger at their melanoma diagnosis than the non-mutated familial melanoma cases. Continue reading
Ubiquitin Proteasome System Targeting for Cancer – Nurix and Celgene
Celgene and Nurix entered into a collaboration to develop small molecule treatments for cancer that target the ubiquitin proteasome system (UPS). Continue reading
Kevetrin – p53 Inducer by Cellceutix
Thioureidobutyronitrile (Kevetrin) is an intravenous drug currently in a Phase 1 study in patients with advanced solid malignancies. It acts by promoting apoptosis in several ways: Continue reading
Monoclonal antibodies + kinase inhibitors are better than antibodies alone in breast cancer and B-cell lymphoma
The combination of Herceptin plus pan-HER (EGFR and Her 2 an 4) kinase inhibitor neratinib resulted in a 33% improvement in progression free survival versus Herceptin alone in breast cancer patients. Rituxan combined with idelalisib, PI3K inhibitor, resulted in a near doubling of progression-free survival at 24 weeks versus Rituxan, alone in patients with Chronic Lymphocytic Leukemia, non-Hodgkin’s Lymphoma, and small cell lymphoma. The news for neratinib tripled the valuation of Puma Biotechnology, while the FDA granted approval of Gilead’s drug Zydelig (idelalisib). Continue reading