Category Archives: Cell Cycle

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

CDK4/6 Inhibitors – Excellent Results Support Paradigm Shift in HR+/HER2- Breast Cancer

We have previously written about CDK4/6 inhibitor, palbociclib (Ibrance) for the treatment of patients with hormone receptor positive (HR+) Her-2 negative (HER2-) disease. In a randomized study of 165 patients who had not been treated previously, palbociclib plus letrozole (a nonsteroidal competitive inhibitor of the aromatase enzyme system that inhibits the conversion of androgens to estrogens) was superior to letrozole, alone: 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

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

Hypomethylating agents are effective in myelodysplastic syndrome

Results of studies in patients with low- and intermediate-risk myelodysplastic syndrome (MDS) treated with hypomethylating agents (low dose azacytidine or decitabine) followed for a median of 18 months were presented at the Society of Hematologic Oncology meeting in Houston on September 9, 2016. Continue reading

Cdc7 inhibitor for the treatment of cancer

ProNai Therapeutics is a Canadian biotech company that recently licensed the rights to a small molecule inhibitor of Cdc7 (cell division cycle 7), a key regulator of both DNA replication and DNA damage response. The drug has shown activity against several cancers in preclinical studies. Continue reading

New data with temozolomide plus radiation for brain cancers

The results of two studies have demonstrated that the use of temozolomide (TMZ) plus radiation increases disease-free and overall survival in patients with glioblastoma and a low grade glioma called anaplastic glioma. 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

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

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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