Category Archives: Genetics

Neratinib for breast cancer – the key is managing gastrointestinal toxicity

Neratinib is an irreversible tyrosine-kinase inhibitor of EGFR (epidermal growth factor receptor), as well as HER1, HER2, and HER4. It is being developed for patients with breast cancer. It blocks many signal transduction pathways that result in proliferation and invasion, leading to cell cycle arrest and apoptosis. (Figures 1 and 2). Continue reading

Photo-immunotherapy approaches for cancer

The NCI (National Cancer Institute) highlighted two photo-immunotherapy (PIT) approaches that employ antibodies conjugated to phthalocyanine dye IRDye 700DX (IR700). 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

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

Mechanisms of Melanoma Resistance to PD-1 Checkpoint Inhibition

It is estimated that about 40 percent of patients with advanced melanoma, the deadliest form of skin cancer, will initially respond to an immunotherapy, but about a quarter of those 40 percent will relapse within three years of treatment. In order to identify the mechanisms by which resistance to PD-1 inhibition is mediated, UCLA researchers studied biopsies of melanoma tumors taken before and after treatment with Keytruda (pembrolizumab) in patients whose cancer had returned. 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

Rociletinib for Resistant Non-Small Cell Lung Cancer Patients with EGFR T790M Mutation – Anthony J. Meglio, Contributor

There are two major subtypes of lung cancer: Non-Small Cell Lung Cancer (NSCLC), which accounts for 85% of all cases,  and Small Cell Lung Cancer (SMLC).  About 60% of NSCLC are unresectable at diagnosis, hence, the poor prognosis – ten to twelve months survival when treated with platinum-based chemotherapy.  Treatment options are evaluated based on the histologic subtype and the presence of mutations to determine the the best combination of molecular therapies for treatment. Ten to twenty percent of patients with NSCLC have a mutated epidermal growth factor receptor, most commonly. a deletion in the in-frame of exon 19 (around amino acid 747 to 752) or a L858R point mutation of exon 21. On June 1, 2016, the FDA approved the first blood test (liquid biopsy) companion diagnostic to determine whether these mutations are present. 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