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
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
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
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.
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
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.
Venetoclax is a novel cancer therapy being developed by Roche and AbbVie. The U.S. FDA has accepted the New Drug Application and granted Priority Review and Breakthrough Therapy Designation for venetoclax for the treatment of people with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, including those with 17p deletion. Continue reading
Two companies announced news last week regarding their efforts to treat cancer by administering treatments that become activated by physiological conditions specific to the tumor microenvironment. Threshold Pharmaceuticals announced data from Phase III clinical trials of evophosphamide (TH-302), and BioAtla announced an antibody development deal with Pfizer. Continue reading
Eli Lilly has licensed exclusive worldwide rights to Ignyta’s Phase I taladegib oncology development program, in a deal the San Diego biotech said could generate up to $53 million-plus. Taladegib is an oral bioavailable small molecule hedgehog/smoothened antagonist. The compound has achieved clinical proof-of-concept and a recommended Phase II dose based on earlier clinical studies. Continue reading