Author Archives: Joseph Gulfo

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 →

Early Cancer Detection Company, Grail, Led by Former Google VP – Ashley P. Angelo, Contributor

Healthcare firm Grail, which has been formed by the gene sequencing company Illumina, named Jeff Huber, former Google X Senior Vice President, as its CEO in February. With Huber’s experience in developing large-scale data, Grail hopes to improve gene sequencing technology used in blood tests for early detection of cancer in asymptomatic patients so that immunotherapeutic strategies, as opposed to toxic chemotherapy, can be employed with the goal of curing cancer. Continue reading →

Celldex’s ADC Glembatumumab-vedotin for Triple Negative Breast Cancer

Antibody drug conjugate Glembatumumab vedotin (GV) is in late phase 2 trials for patients with triple negative breast cancer (TNBC) – those whose tumors do not express estrogen, progesterone, or HER-2. Approximately 15% of breast cancer patients have TNBC; it is an important area of research for both researchers and clinicians alike because: Continue reading →

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.

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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 →

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.

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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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