Hepatocellular carcinoma (HCC) is a primary cancer of the liver that occurs as a result of chronic liver disease, including cirrhosis and hepatitis B and C infections (Figure 1). Serum alpha-fetoprotien (AFP) levels are elevated early in the disease, and screening of patients with chronic liver disease for AFP has lead to earlier diagnosis of HCC. The test is 40-64% sensitive (the ability to detect disease when disease is truly present) because many HCCs do not produce AFP, but it is 75-91% specific (the ability to rule out disease when disease is truly absent) – an AFP of over 400 mg/mL is considered diagnostic. Continue reading
Category Archives: Signal Transduction
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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NQ01 – a new target for cancer therapy
NQO1 [NAD(P)H:quinone oxidoreductase 1 over-expression has been shown to confer a poor prognosis for patients with cancer of the breast, colon, cervix, lung and pancreas. Recent research indicates that the mechanism involves stabilization HIF-1α (hypoxia inducible factor-1) such that it is not degraded. Continue reading
Neratinib for breast cancer – the key is managing gastrointestinal toxicity
Neratinib is an irreversible tyrosine-kinase inhibitor of EGFR (epidermal growth factor receptor), as well as HER1, HER2, and HER4. It is being developed for patients with breast cancer. It blocks many signal transduction pathways that result in proliferation and invasion, leading to cell cycle arrest and apoptosis. (Figures 1 and 2). Continue reading
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
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
Rociletinib for Resistant Non-Small Cell Lung Cancer Patients with EGFR T790M Mutation – Anthony J. Meglio, Contributor
There are two major subtypes of lung cancer: Non-Small Cell Lung Cancer (NSCLC), which accounts for 85% of all cases, and Small Cell Lung Cancer (SMLC). About 60% of NSCLC are unresectable at diagnosis, hence, the poor prognosis – ten to twelve months survival when treated with platinum-based chemotherapy. Treatment options are evaluated based on the histologic subtype and the presence of mutations to determine the the best combination of molecular therapies for treatment. Ten to twenty percent of patients with NSCLC have a mutated epidermal growth factor receptor, most commonly. a deletion in the in-frame of exon 19 (around amino acid 747 to 752) or a L858R point mutation of exon 21. On June 1, 2016, the FDA approved the first blood test (liquid biopsy) companion diagnostic to determine whether these mutations are present. Continue reading
Olaratumab Receives Priority Review for Soft Tissue Sarcoma
The platelet derived growth factor receptor-α (PDGFRα) monoclonal antibody, olaratumab (IMS-3G3) by Eli Lilly, received Priority Review from the FDA on the strength of data from its Phase II trial in patients with soft tissue sarcoma (STS). The drug already received Orphan Drug, Breakthrough Therapy, and Fast Track designations from the agency. Continue reading
FDA Grants Antibody-Drug Conjugate Breakthrough Designation in Triple Negative Breast Cancer – Amani Khawatmi, Contributor
The FDA granted Breakthrough Therapy Designation to Sacituzumab govetican (IMMU-132) for treatment of triple-negative breast cancer (TNBC). A diagnosis of triple negative breast cancer means that the three most common types of receptors known to fuel most breast cancer growth–estrogen, progesterone, and the HER-2/neu gene– are not present in the cancer tumor. This means that the breast cancer cells have tested negative for hormone epidermal growth factor receptor 2 (HER-2), estrogen receptors (ER), and progesterone receptors (PR). Since the tumor cells lack the necessary receptors, common treatments likehormone therapy and drugs that target estrogen, progesterone, and HER-2 are ineffective.