What's new?

Immunodeficiency sets the stage for human herpesvirus 8 (HHV-8) infection, which can lead to Kaposi sarcoma. Compared with the general population, HHV-8 infection is common in HIV-positive individuals and in men who have sex with men (MSM). Those associations are corroborated by the present meta-analysis, which also shows that HHV-8 seroprevalence is highest in MSM and in children. Sexual transmission of HIV and HHV-8 is likely in MSM. In children, who typically acquire HHV-8 via nonsexual transmission, infection may occur as a result of HHV-8 shedding from HIV-positive family members. Further studies are needed to clarify HHV-8 transmission routes.

What's new?

Incidence in esophageal adenocarcinoma has increased sharply among all age groups, with a disconcertingly increasing proportion of advanced-stage tumors occurring at younger (< 50 years) ages. However, the relative rarity of these malignancies has precluded prior studies from assessing risk factors across age groups. Here, by pooling data from 8 case-control studies, the authors find that recurrent heartburn/regurgitation and obesity are appreciably stronger risk factors for early-onset esophageal adenocarcinoma relative to older age-categories. Understanding the mechanisms through which reflux and obesity confer increased risks of esophageal cancer at younger ages might yield important insights for prevention, control, and clinical management.

What's New?

The role of lifestyle factors in the growing numbers of thyroid cancer remains unclear. Here, the authors uncover associations with high total energy intake and low consumption of polyunsaturated fatty acids in a large European cohort (EPIC). They further find positive associations with starch intake and glycemic index only in people with a body mass index equal or larger than 25, possibly implicating an altered insulin response in the etiology of this cancer.

What's new?

A single base pair change in a gene's promoter region can influence cancer progression, according to new results. The L-plastin gene is important for prostate cancer invasion and metastasis, and these authors sequenced the promoter region looking for variable regions. They identified a SNP at position−1687; then they showed that a transcriptional suppressor binds this site. One of the variant sequences helps that suppressor bind more strongly, and that variant showed up more often in healthy individuals and low recurrence risk in those with cancer. Thus, this L-plastin promoter SNP could be a useful indicator for prostate cancer prognosis.

What's new?

DNA methylation profiles may play an important role in the development and progression of breast cancer (BC) subtypes, but the prognostic value of aberrantly methylated biomarkers in distinct subtypes and the role of DNA methylation in distinct gene regions remain controversial. This study assesses the prognostic impact of the expression of aberrantly methylated genes and expression–methylation correlations in BC subtypes. Key methylated prognostic genes were identified, including immune-related genes, particularly in ER−/HER2− tumors. DNA methylation in specific gene regions differentially affects gene expression, supporting the importance of epigenetic biomarkers for prognostication and clinical stratification of patients with distinct BC subtypes.

What's new?

Oral tongue squamous cell carcinoma (OTSCC) is a rare head and neck cancer that typically is asymptomatic in early stages. Hence, in order to improve prognosis in OTSCC, predictive biomarkers that are independent of tumor stage must be identified. Here, using four fluorescence in situ hybridization (FISH) gene probes and the software FISHtrees, phylogenetic tree models of tumor progression in OTSCC patients were constructed. Analyses of the models showed that the more diverse the changes within the four marker genes, the worse the outcome in OTSCC. The markers predicted survival independent of smoking behavior and tumor stage.

What's new?

Genetic mutations that alter mechanisms of DNA repair and genomic maintenance potentially heighten individual susceptibility to cancer. In the present study, this relationship was examined in the context of familial and sporadic breast cancer. Nuclear expression of PARP1, a protein involved in DNA repair, was found to serve as an independent factor for sporadic breast cancer. Meanwhile, nBRCA1 expression was associated with aggressive tumor phenotypes, with potentially important roles in the pathogenesis of both familial and sporadic malignancy. The findings highlight the complexities of aberrant DNA repair in breast cancer and the therapeutic potential of PARP1 inhibition.

What's New?

T-cell large granular lymphocytic leukemia (T-LGL) is often associated with mutations in the STAT3 gene, but associations with other genetic mutations remain unknown. Here the authors identified non-synonymous mutations in the gene encoding TNF-alpha-induced protein 3 (TNFAIP3), a negative regulator of NF-kappa B signaling, in three patients with T-LGL. The study underscores the important role of NF-kappa B activity in this otherwise poorly understood lymphoid malignancy.

What's new?

In cancers associated with Epstein-Barr virus (EBV), the virus persists in latent form, becoming susceptible to drug therapy only after the lytic cycle has been reactivated. To effectively leverage lytic reactivation clinically, however, more specific and more potent pharmacologic lytic inducers are needed. A promising agent is romidepsin, a class I histone deacetylase (HDAC) inhibitor, shown in this study to potently trigger the EBV lytic cycle through HDAC-1/-2/-3 inhibition and protein kinase C-δ activation. Lytic induction augmented the cell-killing effects of the antiviral ganciclovir. The data warrant further investigation of romidepsin for the treatment of EBV-associated cancers.

What's new?

The calcium-sensing receptor (CaSR) suppresses tumor formation in the colon, and its expression characteristically is decreased in colorectal tumorigenesis. In this study, CaSR expression was inversely correlated with the expression of the microRNAs miR-135b and miR-146b. In Caco2/AQ and HT29 colon cancer cells, these molecules targeted the CaSR, and their inhibition was associated with high CaSR expression and reduced cell growth. In colorectal tumor tissue from patients, overexpression of miR-135b and miR-146b was correlated with reduced CaSR expression. Targeting of microRNAs and CaSR re-expression could form the basis for a novel therapeutic approach to colorectal cancer.

What's New?

The steroidal drug fulvestrant is a powerful antiestrogen, blocking the estrogen receptor-alpha to a greater extent than tamoxifen. However, the development of drug resistance is a considerable problem with fulvestrant. For the first time, the authors of the present study examined the biological effects of fulvestrant therapy using sequential breast tumor biopsies from untreated, treated, and relapsed patients. While residual estrogen receptor activity and tumor cell proliferation were detected at relapse, no meaningful increases were found in EGFR/HER2/MAPK activity. Ki67 expression was associated with duration of response, indicating promise as a predictive biomarker for fulvestrant outcome.

What's new?

The distinct ethnic and geographic incidence patterns of nasopharyngeal carcinoma (NPC) occur on a background of complex genetic alteration, with the loss of tumor suppressor genes thought to be of particular consequence. The present study suggests that the loss of IKBB, a putative tumor suppressor in NPC, is critical in the progression of the disease. Experiments show that, acting through the NF-κB/Akt/Gsk3β signalling pathway, IKBB expression suppressed cell migration and angiogenesis. In vivo, IKBB attenuated tumor growth, with important modulatory effects on the tumor microenvironment. IKBB expression was diminished in the majority of patient samples.

What's New?

Squamous cell carcinomas of the head and neck (SCCHN) are not a homogenous group of tumors. This means that biomarkers are urgently needed, so that prognosis and treatment can be individualised. In this study, the authors found that patients with higher levels of CD8+ tumor-infiltrating lymphocytes (TILs) within their tumors had improved outcomes after treatment. These results suggest that CD8-positive TILs may have antitumor activity, and that their expression may be a useful prognostic biomarker for treatment stratification.

Squamous cell carcinoma of the head and neck (SCCHN) represents about 6% of the total cancer incidence and approximately 500,000 new cases are diagnosed each year worldwide. Radical surgery including resection of the primary tumour and neck dissection of regional lymph nodes followed by postoperative chemoradiotherapy (CRT) is commonly performed in locally advanced SCCHN with a 5-year survival rate of 40–60% .

What's new?

About half of all cancers carry mutations in p53, and some cancers also overexpress the oncogenic E3 ligase Mdm2, which normally regulates p53 nuclear export and degradation. Nuclear localization of p53 and Mdm2 have kept the molecules largely beyond the reach of therapeutics, but as this study shows, both can be rendered susceptible to therapies via a combination of bispecific single-chain antibody Fv fragments (scFvs). Bispecific scFvs constructed from mAb 3E10 bound to p53 and restored its function. They also bound to Mdm2, blocking p53 degradation. Combined intracellular antibodies could augment cell-killing effects when used alongside conventional cancer treatments.

What's new?

A new synthetic cytokine could jump-start the immunotherapy route to treating glioblastoma. The cytokine IL-15 has shown promise at stimulating an immune response, but its short half-life in the bloodstream has stymied efforts to deploy it against the deadly brain tumor. This article reports results from tests of a synthetic IL-15 molecule against glioblastoma in mice. They show that the molecule spurs a strong immune defense against the tumors, and a long-term immune memory against recurrence. Clinical testing in humans could be on the horizon.

What's new?

There is mounting evidence that the Notch1 receptor is important in modulating tumor growth and an independent predictor of survival in colorectal cancer (CRC). While mutations in the NOTCH1 receptor have not yet been described in CRC, this study shows that a gain in NOTCH1 gene copy number is associated with worse survival. Targeting cells with a specific Notch1 antibody resulted in potent antitumor growth in a CRC patient-derived tumor xenograft model. A NOTCH1 gene copy number gain may thus be a prognostic marker for disease recurrence as well as a predictive biomarker of sensitivity to a Notch1 targeted therapy.

What's new?

Circulating tumour cells (CTCs) are disseminated malignant cells from which biological and therapeutic information may be obtained non-invasively. Detection of small CTC populations within the large number of normal blood cells is a challenge. This study describes a novel method for the detection and high-resolution imaging of CTCs. Unlike most other studies, CTC detection is not reliant upon expression of a single biomarker. The method is applicable to all cancers; the authors present preliminary results from four tumour types. The high quality of the images allows biological characterisation of the tumour cells and increases the clinical potential of the approach.

What's new?

Telltale methylation may signal poor outcome in ovarian cancer, according to new results. As yet, ovarian cancer patients have limited options for individualized treatment, because no prognostic markers are known. To find some, these authors scanned the genomes of ovarian tumor cells to see whether DNA methylation patterns could be correlated with survival. They found 220 places where the DNA was differentially methylated between patients with good and poor outcomes, as defined by 3 years of progression-free survival. They went on to show that methylation of the genes RUNX3 and CAMK2N1 points to a shorter survival time.

What's new?

A breath test could help diagnose colorectal cancer, according to this new report. Because a breath test is minimally invasive, it could inspire better compliance than colonoscopy. These authors tested volatile organic compounds in breath samples from colorectal cancer cases and controls, using two different methods of analysis. They successfully identified four compounds that accurately identified the cancer patients, establishing a distinctive “breath-print” for colorectal cancer, possibly leading the way to a cheap, effective, non-invasive screening tool.

What's new?

Postmenopausal women with metabolic syndrome (MetS) are at increased risk of breast cancer (BC), as well as poorer prognosis and possibly recurrence. In this study, the authors found that women who adhered to more dietary recommendations for preventing cancer were also less likely to develop MetS. These results warrant further study, as they suggest that following dietary guidelines that reduce MetS might, in turn, reduce the risk of BC and BC recurrence.

What's new?

Fluoropyrimidines are among the most commonly used anticancer drugs. Fluoropyrimidines act by inhibiting thymidylate synthase, encoded by the gene TYMS. A G>C substitution in the promoter enhancer region of TYMS, rs183205964, has been shown to reduce TS activity in vitro, but its effect in patients is unknown. We determined the clinical relevance of this variant as a predictor of severe fluoropyrimidine-induced toxicity in a cohort of 1605 patients treated with fluoropyrimidine-based chemotherapy, and demonstrate for the first time that rs183205964 is associated with risk of early severe toxicity.