Category Archives: Transcription Factors

OLIG2 inhibitor for glioblastoma

OLIG2 (Oligodendrocyte transcription factor-2) is a transcription factor that is expressed in the pMN domain of the ventral ventricular zone in the embryonic spinal cord. Along with OLIG1, it is responsible for the development of motoneurons and oligodendrocytes. Astrocytes and ependymal cells also originate from the pMN domain. 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

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

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

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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Liquid Biopsy from Pathway Genomics – Appropriate Uses

Liquid biopsy is the use of blood to diagnose cancer. Pathway Genomics launched its CancerIntercept test that screens for multiple cancers. Continue reading

Kyprolis versus Velcade in Phase 3 Study in Previously-Treated Patients

In a Phase 3 study of 929 patients with previously treated multiple myeloma, two proteasome inhibitors, Velcade (bortexomib – Johnson & Johnson and Takeda) ) and Kyprolis (carfilzomib – Amgen), in combination with dexamethasone, were compared. Patients treated with Kyprolis had a median progression-free survival of 18.7 months, versus 9.4 months for those treated with Velcade.

Kyprolis versus velcade

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Merck Acquires OncoEthix for Novel MYC Blocker

Last week, Merck acquired OncoEthix at a price of $375 MM for OTX015, a synthetic small molecule which targets the BET bromodomain proteins 2, 3, and 4 (BRD2/3/4). Continue reading