National Ovarian Cancer Awareness month

Long said to be a “silent killer,” ovarian cancer is now understood to display symptoms even during early stages, but those symptoms often are mistaken for gastrointestinal problems or simply signs of aging. Also, while the ovarian cancer rate in the U.S. has been in decline for decades, the actual number of cases and the actual number of deaths have been climbing as a consequence of having an increasingly larger and older population. Therefore, early detection remains a priority, as does developing effective therapies. With all of that in mind, the ASBMB shared stories and studies in September in observance of National Ovarian Cancer Awareness Month.

Decoding ovarian cancer’s dark signaling pathways
Researchers write in a paper in Molecular & Cellular Proteomics about using proteotranscriptomic techniques to uncover associations between factors expressed by high-grade serous ovarian adenocarcinoma and the likelihood of patient survival. Learn more. Read the paper.

A holistic view of ovarian cancer
Researchers in 2016 presented one of the largest studies ever done of the most malignant type of ovarian cancer. Learn more.

Overcoming cisplatin resistance in ovarian cancer cells
In this study in the journal Molecular & Cellular Proteomics, researchers used proteomics to compare protein phosphorylation patterns in chemotherapy-resistant and chemo-sensitive ovarian cancer samples. They found that a protein called sequestome-1 was highly phosphorylated and expressed in different cellular regions in the drug-resistant cancers compared with the vulnerable cancers. In the future, sequestome may serve as a diagnostic marker for chemotherapy resistance.

Credentialing individual samples for proteogenomic analysis
In this study in the journal Molecular & Cellular Proteomics, researchers comparing the genome to the proteome in ovarian cancer found a way to do better quality control, matching RNA to protein levels, to get around a common problem in studying cancer cells.

Working on better diagnostics  
Researchers studying glycosylation, a post-translational modification that changes dramatically in different parts of a tumor, found specific glycans that could indicate whether tissue sample was cancerous or not. They hope to use this technology to improve diagnoses based on biopsies. Read the paper in the journal Molecular & Cellular Proteomics.

Overexpression of phospholipase D in ovarian cancer cells
In this classic paper from the Journal of Lipid Research, researchers found that the enzyme phospholipase D is overexpressed in ovarian cancer cells. In the years since this work was published, phospholipase D has become an important target for drug development.  Read the paper.

Role of lipid in ovarian cancer cells
This classic Journal of Lipid Research study was the first to show a functional role for an unusual type of lipid, known as LPA for short, that promotes cell division and metastasis in ovarian cancer cells.

Exploring the potential of antibodies
Sphingosine-1-phosphate is a lipid elevated in cancers, including ovarian cancer. In this study in the Journal of Lipid Research, researchers reported that they had developed an antibody that could block S1P from binding to its receptor and triggering inflammation. The antibody later became a drug candidate for treating solid tumors, but unfortunately it was not beneficial to patients.

Mechanisms of metastasis
Ovarian cancer cells exhibit an insidious form of metastasis in which aggregates of ovarian cancer cells float in the fluid of the peritoneal cavity before forming secondary lesions. Researchers recently investigated the role of membrane type 1 matrix metalloproteinase in ovarian cancer cells’ ability to invade new tissues. They found that phosphorylation of the matrix metalloproteinase changed cancer cell aggregation and adhesion, suggesting that post-translational regulation of this enzyme may play a key role in ovarian cancer metastasis. Learn more. Read their Journal of Biological Chemistry paper.

Exploring the potential of inhibiting a sugar modification
Tumor suppressor protein p53 was one of the earliest factors identified to play a key role in cancer. The cancer-related roles of protein post-translational modifications with sugars, meanwhile, are only recently beginning to be appreciated. Researchers recently investigated how p53 modification with the sugar O-GlcNAc affected ovarian cancer, in which p53 is often mutated. They reported in the Journal of Biological Chemistry that O-GlcNAcylation affected p53 activation and that inhibiting O-GlcNAcase, an enzyme that removes the modification, impaired tumor cell growth. Read their paper.

What we can learn about ovarian cancer from blood cancers
Inhibiting histone deacetylases (HDACs) has been an effective strategy to treat some blood cancers, but it has been less effective in solid cancers such as epithelial ovarian cancer. Researchers recently reported in the Journal of Biological Chemistry a unique feature of ovarian cells that might explain this discrepancy. In ovarian cancer, HDAC inhibition increased the expression of a chemokine that induces cell proliferation and survival. Targeting this pathway in a combination therapy might  improve HDAC inhibitor effectiveness against ovarian cancer. Read the paper.