What's new?

Early detection of epithelial ovarian cancer (EOC) remains a substantial clinical challenge. The authors built a 3D in vitro model of early stage EOC by expressing known oncogenes in immortalized primary ovarian epithelial cells. They then quantified changes in abundance of secreted proteins using mass spectrometry at the earliest stages of neoplastic transformation. Candidate biomarkers were followed in >200 primary EOCs, and three (API5, CHI3L1, FASN) were associated with high tumor grade in early-stage EOCs, validating the in vitro approach to in vivo biomarkers for this deadly cancer.

What's New?

Although tumor-associated fetal protein AFP has demonstrated utility as a clinical tumor marker, the significance of intracellular AFP remains unclear. This study set to explore the role of cytoplasmic AFP during hepatitis B virus (HBV)-induced carcinogenesis. The results show that HBx promotes transcription of AFP by acting on two elements in the regulatory region of the AFP gene. As a consequence, transcription of the tumor suppressor gene GADD45α is suppressed, through the disruption of RAR signaling. Cytoplasmic AFP is thus not only a histochemical biomarker for human hepatoma but also an intracellular signal molecule and potential participant in HBx-induced hepatocarcinogenesis.

What's new?

Many cells secrete exosomes. These nanoscale vesicles contain signaling molecules, mRNA, and miRNA, and play a critical role in intercellular communication. In this study, the authors identified several angiogenic factors in exosomes from nasopharyngeal carcinoma (NPC) cells. Purified NPC exosomes also caused normal endothelial cells to change to an angiogenic phenotype. These findings shed new light on the mechanisms by which NPC tumors may increase their blood supply, and also suggest that these exosomes may offer a promising therapeutic target.

What's new?

Once breast cancer metastasizes, it is generally incurable. Proteins in the extracellular matrix play a crucial role in launching the tumor cells to a new site. These authors investigated one such protein, tenascin-W, which can be found surrounding not only tumor cells but also in bone tissue. Among other things, they studied how breast cancer cells affected tenascin-W expression. The tumor cells induced bone marrow stromal cells to make more tenascin-W, suggesting that the protein may pave the way for the cancer to spread to the bone.

What's new?

Glioma stem-like cells (GSCs) are a cell subpopulation that is believed to be involved in glioblastoma multiforme tumor initiation and acquired chemoresistance. This study shows that cannabidiol acts on GSCs via the Transient Receptor Potential Vanilloid-2 (TRPV2) channel to induce autophagic-dependent inhibition of proliferation, promotion of differentiation, and sensitization to the cytotoxic effects of alkylating agents. Moreover, the authors identify a transcriptional network that is induced by cannabidiol via the Aml-1a transcription factor and stimulates TRPV2-dependent inhibition of proliferation and promotion of differentiation in GSCs. The results suggest a promising approach for regulating the tumor stem-like cell compartment in glioblastoma.

What's new?

Thyroid cancer shows the highest genetic susceptibility among all cancers with non-Mendelian hereditability. The authors performed a two-step association study involving 1820 cases and 2410 controls in Europe and identify the 9q22 locus near the FOXE1 locus as the most important low-penetrance variation in thyroid cancer. In addition, novel variations at 10q26.12 and 6q14.1 were found associated with risk of the disease in a population-specific manner, underscoring how genetic heterogeneity among populations influences thyroid cancer susceptibility.

What's new?

Changes in transcription factor (TF) expression contribute to genetic and epigenetic abnormalities in cancer. In order to capitalize on those changes and advance diagnostic and therapeutic strategies for cancer, researchers must first find a way to detect and quantify changes in TF activity. Here, TF activity was estimated globally in primary head and neck squamous cell carcinoma (HNSCC) using a novel inferential approach that accounted for gene silencing and loss of heterozygosity and homozygosity. Top-scoring pair biomarkers were identified and linked to human papillomavirus (HPV) status, enabling HPV+ and HPV- HNSCC to be distinguished based on TF activity.

What's new?

Because ovarian cancer is difficult to detect early, it is often fatal. Currently, ovarian cancers are categorized as having “BRCAness” or “non-BRCAness,” depending on the patient's family susceptibility to breast and ovarian cancer; hereditary tumors generally respond better to treatment than sporadic ones. These authors searched the genome to find genes that are overexpressed in ovarian cancer; strikingly, they found different genes were boosted in BRCAness tumors than in non-BRCAness disease. One gene frequently overexpressed in non-BRCAness cancers, BRD4, is already a target gene in other cancers, and could be a useful target for treating ovarian cancer.

What's new?

Only a small percentage of melanoma risk is known to be linked to genetic variants identified by genome-wide association studies. In this study, the authors sought to determine whether variants within multiple pathways might interact to increase this risk. They identified five pathways associated with melanoma, and showed significant interaction between variants at TERF1 and AFAP1L2 loci. Given the key role of TERF1 in telomere biology and its physical interaction with AFAP1L2, these results support a role for telomere dysfunction in melanoma development.

What's new?

The use of fluorescent tracers to identify cancerous cells at tumor margins could improve outcomes for surgery with curative intent. This study describes a newly developed near-infrared fluorescent tracer targeted to carcinoembryonic antigen (CEA), a glycoprotein overexpressed in gastrointestinal cancers. In mice, the fluorescent agent, ssSM3E/800CW, accumulated specifically in tumor cells, enabling the detection and delineation of tumor borders on a clinically relevant timescale. If successfully translated into the clinic, ssSM3E/800CW could facilitate the visualization of cancerous tissue and improve the completeness of surgical resection.

What's new?

Although it is now established that alcohol consumption increases breast cancer risk, many questions remain. Using a prospective study design with 11,576 incident breast cancer cases across 10 European countries, the authors confirmed the increased risk of alcohol on breast cancer development. They further show that women who started drinking before their first full-term pregnancy have a higher risk than women who started afterwards. These effects were observed in hormone-receptor positive and –negative tumors pointing to non-hormonal pathways that need to be further investigated.

What's new?

The human papillomavirus (HPV) vaccine is highly effective in preventing HPV infection and cervical intraepithelial neoplasia which may lead to cervical cancer. In this study, the authors evaluated the impact of a publicly-funded HPV vaccination program in a Canadian province, using data from a centralized cervical-cancer screening program. This ecological analysis found a significant reduction in precancerous lesions in the cohort of young women aged 15 through 22 who had received the vaccine.

What's new?

How H. pylori infection cause cancer in one person but remain harmless in another? And more importantly, can they be distinguished ahead of time, and the cancer halted before it begins? These authors showed that people who tested positive for a multiplex of 15 H. pylori antigens were more likely to develop gastric cancer. They then identified 6 individual antigens which increase the risk of gastric cancer. The multiplex assay, then, may be a useful risk-stratification tool in high risk areas.

What's New?

Primary fallopian tube carcinoma (PFTC) is a rare disease of unknown etiology. Among the suspected risk factors is postmenopausal hormone therapy, regimens of which are linked to ovarian cancer, a disease closely related to PFTC. In this analysis of data from the Finnish Cancer Registry and Prescription Register, both sequential estradiol-progestin therapy and the combined use of estradiol and a levonorgestrel-releasing-intrauterine system were associated with increased PFTC risk among women age 50 or older. Risk rose significantly after the regimens had been used for five years or longer. The study supports the idea of hormonal involvement in PFTC.

What's new?

Previous studies have indicated that environmental or lifestyle factors may be involved in the etiology of renal cancer, and that moderate alcohol consumption may reduce the risk of this type of cancer. In this very large European study (nearly 500,000 subjects), the authors found that, indeed, total alcohol consumption was inversely associated with renal cancer overall (for all subsites combined), and also with cancers of the renal parenchyma.

What's new?

How does obesity confer an increase in endometrial cancer risk? Some studies have suggested that adipokines could be involved, in particular, adiponectin, leptin, and the ratio between the two. Adiponectin is generally associated with anti-diabetic and anti-inflammatory actions, while leptin contributes to cell proliferation and metastasis. In this study, the authors collected the existing literature on adiponectin, leptin, and endometrial cancer risk, and analyzed the combined data. They conclude that increased circulating adiponectin or decreased leptin, or a higher A/L ratio, corresponds to a reduced risk of endometrial cancer.

What's new?

Coffee and tea are surpassed in global consumption only by water, suggesting that any association they might have with cancer is potentially of great magnitude. The present investigation assessed the relationship between coffee and tea consumption and breast cancer risk using data from the Swedish Women's Lifestyle and Health study. Analyses show that women who consumed ≥3 cups of coffee daily were at decreased risk of breast cancer, whereas women who consumed ≥1 cups of tea per day were at increased risk. Coffee may play a role in breast cancer prevention.

What's New?

Women in the Netherlands are supposed to start routine mammograms at 50, but that recommendation is under review. Considering advances in technology and increasing cancer rates among younger women, these authors studied the cost-effectiveness of digital mammography starting before age 50. The current protocol, biennial screening from ages 50 to 74, costs €3,376 per life-year-gained (LYG). Extending biennial screening to 48 year olds, the authors found, cost €5,329 per additional LYG, and beginning at age 45 increased the cost to €7,628 per additional LYG. Thus, earlier screening could be a cost-effective strategy.

What's New?

Inhibitors of topoisomerase 1 (TOP1) are merging as second or third line treatment options for breast cancer but predictive markers for their success are lacking. Here the authors show by fluorescence in situ hybridization using formalin-fixed, paraffin-embedded breast cancer tissue samples that gain of TOP1 gene copy number is frequent in breast cancer cells, thus serving as a potential biomarker to pre-select breast cancer patients for treatment with topoisomerase inhibitors in the future.

What's New?

Enhancer of zeste homolog 2 (EZH2) maintains the stemness of tumor cells and may have a critical role in glioma progression. As a promising therapeutic target in various cancers, there are now several candidate EZH2 inhibitors in the pipeline. The interactions of five of them were explored in this study. Experiments conducted in vitro and in vivo show that EZH2 inhibitors are substrates of ABCB1 and ABCG2, efflux transporters that severely restrict the distribution of drug into the brain. The findings suggest that EZH2 inhibitors are unlikely to play a meaningful role in the treatment of intracranial tumors.

What's New?

Certain types of bacteria naturally home to and invade tumors, where they accumulate and ultimately induce tumor shrinkage. How bacteria act to reduce tumors, however, is still unknown. The work presented here shows that intravenous administration of E. coli to mice bearing CT26 colon carcinomas results in the induction of an immune response involving tumor-specific cytotoxic CD4+ and CD8+ T cells. CD4+ and CD8+ T cells effected neoplasia clearance. The findings could have implications for the design of therapeutic strategies that enhance the immune-inductive, cancer-fighting potential of bacteria.

What's New

Finding ways to thwart drug resistance may be as important as identifying new chemotherapeutics. In ovarian cancer, paclitaxel works well initially, but the cancer often returns, no longer susceptible to paclitaxel. Could this resistance be prevented? This study targeted the P-glycoprotein (Pgp), known for pumping chemotherapeutic agents out of the cell. The authors showed that inhibiting the overexpression of Pgp in cultured ovarian cancer cells thwarts the onset of paclitaxel resistance. Mice bearing ovarian cancers who were treated with paclitaxel and a Pgp inhibitor remained sensitive to paclitaxel, and survived longer than mice treated with paclitaxel alone.