Journal Watch

Discovery offers new insight on lung cancer risk

Researchers have discovered a proteomic “signature” from the airways of heavy smokers that could lead to better risk assessment and perhaps new ways to stop lung cancer before it starts. The findings, reported Nov. 17, 2016, in JCI Insight, are based on the observation that otherwise normal-looking cells in the epithelial lining of the lungs of heavy smokers and others at high risk for lung cancer undergo the same kind of “metabolic reprogramming” as do cancer cells. The research, which is still ongoing, aims to determine if this metabolic reprogramming would be a biomarker for risk as well as an avenue for prevention, said Pierre Massion, M.D.

Study catches ‘notorious’ drug pump in action

Researchers have mapped the conformational changes that occur in a protein “notorious” for pumping chemotherapeutic drugs out of cancer cells and blocking medications from reaching the central nervous system. Their report, published March 13 in Nature, is an important step forward in understanding—and perhaps one day interfering with—the highly dynamic ABC transporter known as P-glycoprotein, said corresponding author Hassane Mchaourab, Ph.D.

Metastatic pancreatic cancer ‘reprograms’ for malignancy

Metastatic pancreatic cancer changes its metabolism and is “reprogrammed” for optimal malignancy, according to new findings reported Jan. 16 in Nature Genetics. It may be possible to reverse the malignant reprogramming to treat metastatic pancreatic cancer, said Oliver McDonald, M.D., Ph.D., lead author of the study. The researchers have identified a compound that reverses the reprogramming and prevents tumor formation in model systems. They demonstrated that blocking the phosphogluconate dehydrogenase (PGD) enzyme genetically or with a pharmacologic inhibitor strongly inhibited tumor-forming capacity. McDonald is working with medicinal chemists at Vanderbilt to develop more potent PGD inhibitors for testing in animal models.

Melanoma study finds new way to enhance targeted therapies

Researchers have found a way to make melanoma cells more vulnerable to targeted anticancer therapy by pairing BRAF-targeted agents with zalcitabine, a drug formerly used to treat HIV/AIDS. The researchers found that zalcitabine made cancer cells more vulnerable to BRAF inhibition. Joshua Fessel, M.D., Ph.D., said the study, published Feb. 16 in Scientific Reports, reflects the aim of the federal “Cancer Moonshot” initiative to achieve a decade’s worth of progress in only five years, in this case by repurposing old drugs for new purposes.

Active surveillance preserves qualify of life with prostate cancer

Faced with negative quality-of-life effects from surgery and radiation treatments for prostate cancer, low risk patients may instead want to consider active surveillance with their physician, according to a study released March 21 in the Journal of the American Medical Association. The study compared the side effects and outcomes of contemporary treatments of localized prostate cancer with active surveillance in order to guide men with prostate cancer in choosing the best treatment for them. The study involved 2,550 men. Three-year survival from prostate cancer was excellent in the study at over 99 percent for patients regardless of whether they chose surgery, radiation or active surveillance. Men with low-risk prostate cancer should consider active surveillance, said David Penson, M.D., MPH.

Study shows how H. pylori spurs protein related to gastric cancer

Chronic infection with Helicobacter pylori bacterium and its associated inflammation are considered the main risk factors for the development of gastric cancer. Previously, Wael El-Rifai, M.D., Ph.D., and colleagues had discovered that DARPP-32 protein, overexpressed in two-thirds of gastric cancers, plays a crucial role in the development of gastric cancer and resistance to anticancer drugs. Now in a study published Sept. 2, 2016, in Gut, El-Rifai and colleagues show that H. pylori infection turns on the transcription of this protein through activation of the pro-inflammatory NF-kB transcription factor. They show that the infection helps these inflamed cells survive cell death through upregulation of DARPP-32.

Targeting the ‘un-targetable’

Triple negative breast cancers (TNBC) are so named because they lack common genetic target mutations that can be easily treated with specific cancer drugs. However, in a study published Aug. 15, 2016, in Molecular Cancer Therapeutics, Deborah Lannigan, Ph.D., and colleagues investigated a new target involved in TNBC called RSK. They demonstrated that RSK can help cancers metastasize more quickly. By blocking the RSK protein with a novel drug, the researchers were able to prevent cancers from metastasizing. Current treatments to prevent metastasis, known as MEK inhibitors, activate the protein AKT, which can limit their effects. This new drug does not activate AKT, making it a potential new tool against metastatic breast cancer.

Nanobeam lights up colon tumors

The advent of colorectal cancer (CRC) screening, notably colonoscopy, has reduced deaths from this malignancy by 30 percent. Unfortunately, colonoscopy misses about 24 percent of small and flat polyps, which often develop into aggressive forms of CRC. Wellington Pham, Ph.D., and colleagues reported March 2 in International Journal of Nonmedicine that a novel fluorescent nanobeam can discern normal from pathological tissues in freshly biopsied human colonic specimens.