Category Archives: Biology

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 →

Olaratumab Receives Priority Review for Soft Tissue Sarcoma

The platelet derived growth factor receptor-α (PDGFRα) monoclonal antibody, olaratumab (IMS-3G3) by Eli Lilly, received Priority Review from the FDA on the strength of data from its Phase II trial in patients with soft tissue sarcoma (STS). The drug already received Orphan Drug, Breakthrough Therapy, and Fast Track designations from the agency. 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 cancer,  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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The Warburg Effect: Multiple Proposed Roles in Cancer – Conor McAuliffe, Contributor

In the 1920’s Otto Warburg first discovered that tumor cells bypass normal cellular respiration i.e. glucose converted to pyruvate through glycolysis, and the sequential oxidation of pyruvate through the Krebs Cycle in the mitochondria. Instead tumor cells divert pyruvate to lactate dehydrogenase (LDH), which reduces pyruvate into lactate. This type of metabolism, referred to as The Warburg Effect, is normally observed in cells in hypoxic or anaerobic environments, in cells that are proliferating, or in cells in which the accumulation of pyruvate exceeds the capacity of the mitochondria.  Continue reading →

Three Recent Late Stage Disappointments for Lung Cancer, Pancreatic Cancer, Sarcoma, and Glioblastoma

In the last several months, three novel drugs that we have been following on this blog failed in late stage clinical trials. The drugs have diverse mechanisms of action:

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Halaven Shows Survival Advantage in Liposarcoma – FDA Approved

Halaven (eribulin mesylate) was approved by the FDA for the treatment of patients with unresectable or advanced liposarcoma. The treatment is approved for patients who previously had undergone chemotherapy with an anthracycline drug. It was previously approved for patients with breast cancer who had undergone at least two prior chemotherapeutic regimens, including an anthracycline and a taxane. 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 →