Category Archives: Gene Regulation / Gene Control

MDM2 and MDMX inhibitor restores p53 functioning in cancers with wild-type p53

P53 is a tumor suppressor gene that pauses cell division to allow for repair of gene damage, and triggers apoptosis if the damage is not reparable. Loss of p53 is a critical step in the evolution of cancer. Most frequently, p53 is mutated at its DNA binding domain; since p53 is a transcription factor, a diminished ability to bind to DNA significantly disrupts its functioning. 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

Etinostat blocks Treg activity via FOXP3 suppression

Histone deacetylase (HDAC) inhibitors block the removal of acetyl groups from histone proteins. Since acetylation of histones puts chromatin in a more favorable condition for transcription, HDAC inhibitors maintain this favorable state. HDAC inhibitors have been approved for use in cutaneous T-cell lymphoma. They act by sustaining transcription of tumor suppressor genes, which leads to cell cycle arrest and apoptosis. Continue reading

Intra-tumor heterogeneity leads to sampling bias and biomarker failure – Conor McAuliffe, Contributor

A growing understanding of genetic variation both between histologically similar tumors from different patients and within individual tumors themselves is shedding light on the difficulties in treating cancer and developing biomarkers to diagnose it. It has long been known that a single tumor displays differences in morphology, nuclear shape, proliferation, and proportions of constituent cell types. However, these differences may be only be the “tip of the iceberg” as vast genetic and epigenetic variations that underlie them have been discovered between and within tumors. Continue reading

The Roles of P53, BRCA1, and PTEN in Hereditary Cancers – Lauren Fitzgerald, Contributor

Cancer results from accumulated mutations in the cancer cell’s genome. These mutations can occur spontaneously in any cell throughout an individual’s lifetime, often increasing with age or exposure to carcinogenic or mutagenic compounds. These are called somatic mutations that do not exist in every cell, and cannot be passed along from one generation to the next. However, in approximately 5 to 10% of all cancer cases, mutations are passed along through the germ line and can predispose an individual to various types of cancers. 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

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

Targeting Cancer Stem Cells – OncoMed’s R-SPONDIN LGR Antibody for Colorectal Cancer

OncoMed initiated a Phase I/II trial of its anti-RSPO3 antibody (OMP-131R10) in patients with relapsed colorectal cancer. Patients will also be receiving FOLFIRI (5-FU, irinotecan, leucovorin). Continue reading