What's new?

Inflammation can alter the expression of specific proteins, and in the context of head and neck squamous cell carcinoma (HNSCC), which involves a high degree of inflammation, those changes may be of diagnostic or prognostic significance. Here, reduced expression of calcium-binding S100/calgranulin proteins was found to be a common feature of oropharyngeal SCC. Moreover, simultaneous low protein expression of S100A8 and S100A12 in tumor cells was an independent risk factor for unfavorable overall survival. The regulation and function of S100/calgranulins likely is context-dependent, with differences between mucosal and squamous epithelia.

What's New?

Evidence suggests that STAT5b, a member of the signal transduction and activator of transcription (STAT) family, may be of significance in glioma, possibly driving glioma progression from low-grade to high-grade. Analyzing data from The Cancer Genome Atlas (TCGA), the authors of the present report show that STAT5b expression is correlated with proneural glioblastoma (GBM). Modeling of STAT5b expression with platelet derived growth factor B (PDGFB) in a proneural model of murine glioma revealed that STAT5b promotes malignant degeneration to high-grade glioma and decreases tumor-free survival. The tumor-promoting activity was mediated through the anti-apoptotic effect of STAT5b.

What's new?

Gene expression can be effectively turned on or off by addition or removal of acetyl groups. “Reader” proteins, such as the BET family of proteins, respond to these acetylation cues by recruiting transcription machinery. In this paper, the authors show that a BET protein inhibitor, JQ1, slows the growth of osteosarcoma cells in vitro, but wasn't too effective against tumors in vivo. That is, until they tried it in combination with rapamycin: in conjunction with that drug, JQ1 killed off OS cells both in vitro and in vivo, making it potentially useful as a treatment.

What's New?

Prostate cancer turns deadly when it metastasizes and the removal of available androgens – castration -- can no longer hinder it. In this paper, the authors report that the kinase Tpl2 spurs this transition to metastasis. Not only did they find more Tpl2 mRNA in metastatic cells than in non-metastatic, they also showed that Tpl2 upregulates two signaling pathways integral to metastasis. The kinase activity of Tpl2 also support the development of stem cell capabilities in the cancer cells. These results suggest that targeting Tpl2 could impede the spread of prostate cancer.

What's new?

Fatty acid synthase (FASN)—which is overexpressed in cancer and regulates oncogenic de-novo-lipogenesis—has been regarded as a marker of malignancy. Contrarily to the widely accepted concept that normal cells are negative for FASN, here the authors demonstrate that FASN is overexpressed in the ovarian system when cells reveal high growth rates, irrespective of their state of malignancy/differentiation/senescence. FASN thus represents a metabolic marker of ovarian cell proliferation rather than cancer. The study further shows that FASN is a useful cancer target, since quiescent normal cells usually lack it and the few positive dividing normal cells are spared by FASN-drugs.

What's New?

A large number of molecular variations are associated with breast cancer, which has inspired the development of a variety of multigene prognostic tests. However, because those tests are based on small, heterogenous data sets, with the intention of being applicable across breast cancers, their predictive performance is limited. This study describes a dynamic, case-specific approach for prognostic predictor discovery that is based on large, homogenous training sets of data. Training sets were selected for their molecular similarity to test cases. Prognostic accuracy was higher for the dynamic approach than for the genomic surrogates of common multigene assays.

What's new?

Many tumors afflict females less often than males, both in humans and rodents. Understanding why this is so will help direct the creation of targeted prevention measures particularly for tumors that don't respond well to conventional treatments. This paper reports the results of fine mapping a genetic (Mss4) locus that contributes to female rats' resistance to malignant peripheral nerve sheath tumors (MPNST). The authors show that resistance alleles of Mss4 enhance the expression of Schwann cell differentiation- associated genes in females reflected by attenuation of cancer risk. A gene within this locus, Esr2, could be a candidate for future study.

What's New?

While our understanding of the molecular pathways that lead to malignant melanoma has increased over the past few years, it is still incomplete. In this study, the authors identified two new pathways: one that involves WNT signaling (involved in melanoblast development), and another that involves vesicular trafficking (involved in changes in pigmentation phenotype). These results may be useful in developing screening tests for people who are genetically susceptible to melanoma. In addition, the whole-exome sequencing techniques used in this study may aid researchers in identifying mutations in unknown disease-candidate genes.

What's new?

Lipopolysaccharide (LPS) is a critical virulence factor of the bacteria H. pylori, fueling persistent inflammation and gastric carcinogenesis. The authors uncover a novel positive feedback loop involving downregulation of microRNAs miR-375 and miR-106b, which promotes H. pylori LPS-induced activation of the JAK/STAT3 pathway in gastric epithelial cells. MiR-375 usually activates expression of MDM2, which via the transcription factor p63 controls expression of the microRNA-processing enzyme Dicer, thus reinforcing the downregulation of both microRNAs in LPS-treated cells. The authors suggest testing whether MDM2 levels could serve as new diagnostic or prognostic markers in H. pylori-positive gastric cancers.

What's New?

The prognosis and clinical course of low-grade gliomas (WHO grade II) seem to be unpredictable. A technique called “Dynamic O-(2-[¹⁸F]fluoroethyl)-1-tyrosine (¹⁸F-FET) positron emission tomography (PET)” has identified three distinct time-activity curve (TAC) patterns among these tumors. In this study, the authors found that each of these TAC patterns is associated with a different prognosis. TAC analysis might, therefore, be useful as an independent imaging biomarker, offering the prospect of personalized diagnostic and therapeutic strategies for grade II gliomas.

What's new?

Non-small cell lung cancer (NSCLC) is a deadly disease, with fewer than 15% of patients still alive five years post-diagnosis. But as this study suggests, predictive biomarkers could inform the development of much-needed novel therapeutic strategies. Defective expression of the tumor suppressor coiled-coil-domain containing 6 (CCDC6) was correlated with patient survival and, in NSCLC cells, was associated with deficient homology-directed repair (HDR), rendering the cells resistant to cisplatinum but sensitive to the PARP inhibitor olaparib. When given in combination, however, the two agents were synergistic. Thus, CCDC6 levels may offer valuable insight for therapeutic decisions in NSCLC.

What's New?

Circulating tumor DNA (ctDNA) has shown promise as a prognostic biomarker. In this study, the authors compared detection rates and prognostic value of ctDNA versus circulating tumor cells (CTCs) in the plasma of metastatic triple-negative breast cancer (TNBC) patients. The ctDNA was detected more frequently than CTCs. However, while CTC numbers were correlated with prognosis, baseline ctDNA levels were not. This suggests that ctDNA might be more useful in identifying mutations that could provide therapeutic targets than as a prognostic biomarker.

What's new?

Genetic variants involved in prostate cancer are promising candidate biomarkers of clinical outcome, particularly mortality. Previous investigation identified 22 germline variants associated with lethal prostate cancer. Here, analysis of those variants in high-risk patients from families with hereditary prostate cancer validates the association of three single nucleotide polymorphisms (SNPs) with lethal disease. The validated SNPs were located in the genes RNASEL, XRCC1, and AKT1. The findings indicate that germline SNPs may provide prognostic information for distinguishing patients who are at increased risk for progression to fatal prostate cancer.

What's new?

Hereditary factors are responsible for as many as 40 percent of early-onset cases of prostate cancer (PC). Targeting men with a family history of early-onset disease through selective prostate-specific antigen (PSA) screening could improve screening outcomes. This study shows, however, that men who have a first-degree relative with PC are more likely to be diagnosed with PC in the period of time between screenings than they are at the time of screening. Frequency of low-grade tumors and lack of difference in mortality between those with or without family history further indicate that selective PSA screening would be ineffective.

What's New?

A diet rich in anti-oxidants may protect from breast cancer but studies focusing on individual antioxidant intake have been notoriously inconsistent. Here the authors assessed the overall dietary antioxidant capacity in more than 3000 postmenopausal Dutch women by calculating the so-called ferric acid reducing antioxidant potential (FRAP). They show that high dietary FRAP, but not individual anti-oxidant intake, is associated with an overall lower risk of breast cancer, a result that may help design more consistent studies of anti-oxidant intake and cancer risk in the future.

What's New?

Trends in thyroid cancer incidence and mortality vary widely by country, but for most areas of the world, the data indicate an upward trend in incidence and a downward trend in mortality. Those trends are supported by the present analysis of thyroid cancer mortality and incidence globally. The analyses are based on data maintained by the World Health Organization (1970–2012) and Cancer Incidence in Five Continents (1960–2007). The authors attribute the rise in thyroid cancer incidence to increased detection of the disease and the decline in mortality to changes in diagnosis, treatment, and risk factor exposure.

What's new?

Are throat cancers on the rise in Denmark, as in other Western populations? These authors analyzed samples from the Danish Head and Neck Cancer Group, making this the largest non-selected cohort of tonsillar cancer cases studied to date. They found that during the years 2000–2010, the rate of tonsillar cancer increased, and that HPV could be to blame. The incidence of HPV-positive cancers rose over the study period, with most of the HPV-positive cancers harboring HPV-16. When they classified the tumors by whether they originated in the tonsillar tissue, they found that tumor origin was the strongest predictor of HPV status; specified tonsillar tumors contained HPV more often than those appearing to have originated elsewhere.

What's New?

Smoking, everyone knows, is bad for your lungs. But could it also boost a woman's risk of breast cancer? No consistent epidemiological picture yet exists for how smoking affects breast cancer. These authors made use of a large cohort, the Canadian National Breast Screening Survey, to correlate smoking habits with breast cancer risk. They found a strong link between smoking and breast cancer. Timing of cigarette exposure was important; beginning a smoking habit at a younger age, and continuing to smoke for more years, had a larger impact on breast cancer risk, as did number of cigarettes smoked per day.

What's new?

Steady gains in patient survival following the recurrence of tumors in colorectal cancer have brought into question the reliability of mortality as a surrogate of disease outcome. This study examined the ability of a newly developed algorithm to identify colorectal cancer recurrences using routinely collected registry data. The algorithm correctly identified 60 out of 63 recurrences in a Danish cohort of 355 patients under active surveillance. In cumulative incidence curves, it revealed an increased incidence of imputed recurrence in patients with regional versus local disease. The algorithm is applicable to settings where electronic health data are available.

What's New?

Pancreatic cancer kills almost everyone it strikes; just 5% of patients survive beyond 5 years. The best treatment is surgery to resect the tumor, but some patients fail to improve even after pancreatectomy. These authors wanted to find a way to know before surgery whether a patient would likely improve afterward. They analyzed eight tumor markers from 1,000 patients and correlated these markers with patient outcomes. Patients with a particular serum signature, comprising three markers, showed no improvement after tumor resection. Thus, this marker signature could help physicians decide whether to advise surgery.

What's new?

Antibody therapy of solid cancers is well established, but suffers from unsatisfactory tumor penetration of large immunoglobulins or from low serum retention of antibody fragments. Oncolytic viruses are emerging anti-cancer agents that show suboptimal potency due to limited virus spread within tumors. This study establishes an oncolytic virus that genetically delivers a small antibody-based biotherapeutic—an immunoRNase—to tumors. The combined approach addresses barriers to both viral spread and antibody penetration through the expression of small antibody-derivatives inside the tumor that leads to targeted bystander killing and enhanced therapy. Such viro-antibody therapy platform offers interesting opportunities for personalized cancer therapy or targeting of heterologous tumors.