Category Archives: Genetics

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.

Continue 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.

Continue reading →

Melanocytes Must Regain Primitive, Early Embryologic State to Develop Melanoma

Researchers working with the zebrafish melanoma model have determined that oncogene activation and crippling of tumor suppressors genes is not sufficient to transform melanocytes into melanoma cells. It is essential that the cells re-acquire primordial characteristics, as well. Continue reading →

BET Bromodomain Inhibition in Prostate Cancer Treatment

BET bromodomain inhibitors are epigenetic regulators that act by repressing expression of oncogenes, including MYC and BCL-2, that are aberrantly highly expressed in many cancer cells, resulting in inhibited cell proliferation and induction of apoptotic cell death. Continue reading →

Priority Review for Potent Novel Therapy for Chronic Lymphocytic Leukemia (CLL)

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 →

Biomarkers for Wnt activation Predict For HER-2(-) Breast Cancer and NSCLC Response to Vantictumab

OncoMed is developing several compounds that target Wnt and Notch pathways, which are important in cancer and cancer stem cell maintenance, survival, and proliferation. Biomarkers for response of Her-2-negative breast cancer and non-small cell lung cancer (NSCLC) following treatment with Vantictumab, anti-Wnt monoclonal antibody, have been developed. Continue reading →

Tazemetostat Histone Methyltransferase Inhibitor for Hematologic and Solid Tumors

Tazemetostat is a small molecule inhibitor of EZH2 being developed by Epizyme, Inc for the treatment of patients with Non-Hodgkin Lymphoma, including germinal center and non-germinal center diffuse large B-cell lymphoma and follicular lymphoma, as well as genetically-defined solid tumors. In many human cancers, misregulated EZH2 enzyme activity results in misregulation of genes that control cell proliferation—without these control mechanisms, cancer cells are free to grow rapidly.  Continue reading →

ROCA Ovarian Cancer Test for Early Detection

Each year, about 20,000 women in the United States get ovarian cancer. Among women in the United States, ovarian cancer is the eighth most common cancer and the fifth leading cause of cancer death, after lung and bronchus, breast, colorectal, and pancreatic cancers. In 2012 (the most recent year numbers are available)— 20,785 women in the United States were diagnosed with ovarian cancer, and 14,404 women in the United States died from ovarian cancer. Continue reading →