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
Category Archives: Signal Transduction
Pancreatic cancer – early detection, immune response, and infection-based resistance
Approximately 1.6 percent of men and women will be diagnosed with pancreatic cancer at some point during their lifetime. In 2014, an estimated 64,668 patients were living with the disease. The five-year survival for pancreatic cancer is 8.2% and it is projected to be the second leading cause of death due to cancer (behind lung cancer) in the US by the year 2030. For good reason, then, November is Pancreatic Awareness Month. Several recent research items are of particular interest to us. Continue reading
MET – an ideal target for antibody drug conjugate therapy, plus nivolumab
MET is a gene that encodes a receptor tyrosine kinase that is activated upon binding with hepatocyte growth factor (HGF, or Scatter Factor). Specifically, MET is a Continue reading
Anti-APRIL Antibody BION-1301 for Multiple Myeloma
Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow. Plasma cells are B lymphocytes (B-cells) that have been activated to produce immunoglobulins. When plasma cells become cancerous, the produce copious amounts of immunoglobulins and proliferate in the bone marrow, causing crowding-out of other essential hematopoietic cells, leading to reduced numbers of functioning white blood cells (leukopenia leading to immunosuppression), red blood cells (anemia), and megakaryocytes (thrombocytopenia). Continue reading
CLEC12A – a novel target for AML and MDS
CLEC12 (C-Type Lectin Domain Family 12 Member A) is negative regulator of granulocyte and monocyte functioning. It is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. It is also known as Myeloid Inhibitory C-Type Lectin-Like Receptor and Dendritic Cell-Associated Lectin. CLEC12 is a cell surface receptor that modulates signaling cascades and mediates tyrosine phosphorylation of target MAP kinases. Continue reading
Sitravatinib plus nivolumab in NSCLC
Sitravatinib (MGCD516) is an oral multi-tyrosine kinase inhibitor being developed by Mirati Therapeutics. Last week, the company announced that three of eleven patients with non-small cell lung cancer (NSCLC) with genetic alterations in MET, AXL, RET, TRK, DDR2, KDR, PDGFRA, KIT or CBL who were resistant to checkpoint [anti PD-(L)1 therapy] had confirmed partial responses; because of this, dosing in the 34-patient expansion cohort will proceed. Continue reading
OLIG2 inhibitor for glioblastoma
OLIG2 (Oligodendrocyte transcription factor-2) is a transcription factor that is expressed in the pMN domain of the ventral ventricular zone in the embryonic spinal cord. Along with OLIG1, it is responsible for the development of motoneurons and oligodendrocytes. Astrocytes and ependymal cells also originate from the pMN domain. Continue reading
ALK-positive lung cancer – antibodies to fusion protein
Approximately 7% of patients with non-small cell lung cancer (NSCLC) possess a transgene that results from an inversion of chromosome 2 that juxtaposes the 5’ end of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the 3′ end of the anaplastic lymphoma kinase (ALK) gene, resulting in the novel fusion oncogene EML4-ALK . Continue reading
Blocking Protein-Protein Interactions in Cancer
The last twenty years has been an unprecedented time in biology – in sequencing the genome and studying the functions of proteins, as well as in unraveling signal transduction pathways, the fundamental biology of normal and diseased cells has been elucidated to a great extent. Although many druggable targets have been identified, it has largely been impossible to target protein-protein interactions (PPI) in drug development. In fact, only ONE drug that targets a PPI has been approved. Continue reading
Metformin improves cancer outcomes
Metformin (Glucophage) is an antihyperglycemic agent that lowers hepatic glucose production, improves peripheral glucose uptake and utilization, and does not cause increased insulin secretion. In fact, “with metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.” These properties have spawned a great deal of interest in metformin as a treatment for several types of cancers. Continue reading