Category Archives: Apoptosis

Ubiquitin specific protease 7 – a good target for cancer therapy

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

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

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

Inhibition of Nuclear Export Protein XPO1 in Cancer

Selinexor (KPT-33) is a drug that inhibits exportin 1 (XPO1 and CRM1), a nuclear transport protein that shuttles nuclear proteins through the nuclear pore and is responsible for the removal of proteins from the nucleus: 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.
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Engineering safety into CAR T-cells to address toxicities

Adoptive immunotherapy with engineered T-cells, for example, CAR T-cells (Chimeric Antigen Receptor) is associated with significant toxicities including cytokine release syndrome, neurologic toxicity, “on target/off tumor” recognition, and anaphylaxis. CAR T-cells lack the ability to respond to signals that maintain immune homeostasis. For this reason, they are effective relentless killers of cells that express the target to which they have been programmed, however, at a safety cost. Continue reading

SOR-C13 and Psaptides for Ovarian Cancer

The U.S. Food and Drug Administration (FDA) has granted orphan-drug designation to peptide SOR-C13 (Sorcimed) for the treatment of ovarian cancer. Additionally, two forms of a peptide derived from a naturally-occurring human protein (Psaptides) can force tumors to shrink significantly in an animal model of metastatic ovarian cancerContinue reading

Saliva Test to Detect EGFR Mutations and Guide Therapy in Lung Cancer

A new technology called electric field–induced release and measurement (EFIRM) is able to detect biomarkers in saliva for non-small cell lung cancer (NSCLC). The test detects circulating tumor DNA (ctDNA). It is able to detect actionable EGFR (epidermal growth factor receptor) mutations in NSCLC patients with 100% concordance with biopsy-based genotyping, Dr Wong (study author) said, and it can detect the most common EGFR gene mutations that are treatable with TKIs (tyrosine kinase inhibitors), such as gefitinib (Iressa, AstraZeneca Pharmaceuticals LP) or erlotinib (Tarceva, Genentech/Roche). Continue reading

Additional Drivers and Pathways in Basal Cell Carcinoma

The Sonic hedgehog (Hh) pathway is known to be important in basal cell carcinoma (BCC), which as an extremely common skin cancer that only rarely invades and metastasizes. An approved drug for patients with advanced BCC, Vismodegib (Erivedge), interferes with the Hedgehog pathway. The Patched (12 membrane-spanning receptor protein) normally disables Smoothened (7 membrane-spanning protein) rendering it functionally inert. This maintains transcription factor Gli in a cleaved state, acting as a transcriptional repressor. When Hedgehog proteins bind to Patched, Smoothened is released and protects Gli from cleavage. Uncleaved Gli travels to the nucleus and is an inducer of transcription, increasing Cyclin D1 and stimulating the cell cycle (proliferation). Vismodegib blocks the actions of Smoothened. It is administered orally in 150 mg capsules.

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Vanquish Oncology – Procaspase 3 Activation Factor to Selectively Induce Apoptosis

Procaspase-3 is an executioner protein catalyzes the hydrolysis of more than 100 protein targets. These cleavage events ultimately lead to cell suicide, or apoptosis. Caspase-3 is triggered by the intrinsic and extrinsic apoptosis cascades. Continue reading