What's new?

The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising worldwide; however, risk-oriented tumor surveillance guidelines for noncirrhotic NAFLD patients is lacking. In this population-based cohort study, the 10-year cumulative incidence of liver cancer among noncirrhotic NAFLD patients was low overall (2.7%). However, marked differences were found among older patients with elevated serum alanine transaminase levels (highest incidence) and younger patients without liver enzyme elevation (lowest incidence). This points to the usefulness of tumor surveillance in older NAFLD patients with or without liver enzyme abnormalities.

What's new?

This study provides additional cancer statistics of China based on a large national prospective cohort-the China Kadoorie Biobank (CKB). The results indicate that the cancer burden of China for populations aged 35–74 years was probably underestimated. Moreover, we also found significant differences for incidence, mortality and profile of cancer in urban and rural areas of China, suggesting the value of different cancer control strategies for urban and rural areas in the future.

What's new?

The aetiology of childhood leukaemia remains largely unknown. Several hypotheses involve environmental exposures that could implicate spatial clustering of cases. Previous clustering studies are inconclusive, however. This nationwide investigation of spatial clustering of childhood leukaemia is unique in that it used precise geocodes of residence and carefully adjusted for multiple tests. Overall, no evidence of spatial clustering was found. Although individual tests did indicate clustering and a small cluster of acute lymphoblastic leukaemia was identified, Monte Carlo simulations showed that such results could easily arise by chance. This highlights the importance of appropriately accounting for multiple testing in clustering studies.

What's new?

Disparities in cancer risk persist worldwide. Here, the authors analyzed global trends in stomach cancer incidence over time. They find overall a favorable trend possibly due to a decline in lifestyle and environmental risk factors such as Helicobacter pylori infections over successive generations. However, in some countries, the declines are less marked stressing the wide differences among countries.

What's new?

Patients with melanoma on the trunk, scalp and neck generally have poorer prognosis than those whose cancers appear on the extremities or face. To further refine predictions, these authors further classified anatomic locales both by presumed UVR exposure and visibility upon skin self-examination. Melanomas on regions receiving chronic and moderately intermittent UVR exposure had better outcomes than those in highly intermittent exposure sites. A favorable outcome also correlated with cancers in skin sites that were easily, compared to poorly, visible to the patient.

What's new?

Two polymorphisms have been identified in DNA repair pathways that affect the recurrence risk of oral cancer. Cases of squamous cell carcinoma of the oropharynx (SCCOP) are on the rise, partially due to increasing rates of HPV infection, and these cancers frequently come back after treatment. In this study, the authors investigated polymorphisms in miRNA binding sequences in DNA damage repair genes, seeking a genetic explanation for recurrence risk. They found that patients, particularly those positive for HPV-16, carrying variant genotypes in BRCA1 rs12516 and RAD51 rs7180135 had better disease-free survival and lower recurrence rate than those carrying homozygous genotypes.

What's new?

Although Lynch syndrome is known as an inherited cancer syndrome causing colorectal and endometrial tumors at a young age, more than half of the affected individuals do not carry the expected germline mutations in mismatch repair genes. Here the authors comprehensively analyzed the germline and somatic mutational status of patients with suspected Lynch syndrome. They confirm marked heterogeneity in the underlying mutations and molecularly classified up to 86% of the cases, underscoring the need for a comprehensive analysis to allow meaningful genetic counseling and follow-up.

What's new?

Personalized medicine will soon improve treatment for many cancers. However, it's also important to identify high-risk subgroups that are unlikely to be cured with current therapies. In this study, the authors found that mutations in the TP53 gene may help predict the survival of patients with aggressive B-cell lymphomas, regardless of treatment. TP53 mutations should thus be included as a prognostic biomarker in the development and assessment of risk models for B-cell non-Hodgkin lymphoma.

What's new?

Hepatic metastasis constitutes the final stage of pancreatic cancer and is associated with extremely poor prognosis. To improve detection and treatment of hepatic metastasis, however, greater understanding of the regulatory mechanisms driving dissemination to the liver is needed. Here, the authors reveal an association between complement component 1, q subcomponent-binding protein (C1QBP) expression and hepatic metastasis in pancreatic cancer patients. Specifically, C1QBP was found to interact with cell adhesion variant CD44v6 in lipid rafts and thereby regulate insulin-like growth factor-1 signaling pathways, enhancing metastatic potential. The findings highlight C1QBP as a promising therapeutic target for hepatic metastasis in pancreatic cancer.

What's new?

Cancer cells that express the T-cell inhibitory molecule programmed death-ligand 1 (PD-L1) readily escape immune attack. In addition, PD-L1 expression contributes to chemoresistance and is associated with epithelial-to-mesenchymal transition, a process that generates cancer stem cells (CSCs). This study shows that in breast cancer, PD-L1 expression further plays a direct part in maintaining CSC stemness. In breast cancer cells, PD-L1 expression sustained stemness factors OCT-4A and Nanog, via a PI3K/AKT-dependent pathway, and promoted expression of the stemness controlling factor BMI1, independent of PI3K/AKT. Targeting PD-L1 could help advance breast cancer therapy, owing to impacts on the pool of breast CSCs.

What's new?

Alpha-fetoprotein (AFP) plays a critical role in the regulation of tumour growth and progression, during which it interacts with multiple signaling molecules, including caspase-3. In this study, in human hepatocellular carcinoma (HCC) cells, AFP was found to inhibit caspase-3 by interacting primarily with caspase-3 loop-4 amino acid residues Glu-248, Asp-253, and His-257. Modeling analyses showed that the interaction was effected by AFP wrapping around the caspase-3 active site, thereby preventing the activation of apoptosis via caspase-3 interaction with caspase-activated deoxyribonuclease. AFP and the described caspase-3 residues may be valuable targets in the development of novel HCC therapies.

What's new?

p53 mutation is rarely detected in ccRCC, but these tumors are highly resistant to chemotherapies. Here, the authors found that ASPP1 suppression is significantly associated with higher grade and poorer survival of ccRCC. Restore ASPP1 inhibits ccRCC proliferation, and also improves ccRCC's sensitivity to the conventional chemotherapeutic drug 5-FU via specifically activating p53's transcriptional activities toward apoptosis. The findings provide insight into the capability of ASPP1 for overcoming ccRCC resistance by re-activating p53-dependent pro-apoptosis activity.

What's new?

In this report, we demonstrate for the first time that tumor CD70 expression in GBM is involved in tumor progression by increasing the capability of tumor migration/invasion and proliferation, and by promoting the immunosuppressive tumor microenvironment via attracting tumor-associated macrophages (TAM) to the tumors. These results provide a strong rationale for the use of CAR redirected T cells in patients with CD70-positive gliomas. Tumor migration/metastasis and immunosuppression are two major and usually coexisting obstacles for effective cancer therapy. Here, the authors investigate how CD70 expression by glioblastomas (GBM) affects the characteristics of tumor cells and the tumor microenvironment. They demonstrate for the first time that tumor CD70 expression in GBM is involved in tumor progression by increasing the capability for tumor migration/invasion and proliferation, as well as in promoting the immunosuppressive tumor microenvironment by attracting tumor-associated macrophages to the tumors. These results provide a strong rationale for the use of chimeric antigen receptor-redirected T cells in patients with CD70-positive gliomas in the future.

What's new?

Cancer immunotherapy through antigen selection is difficult to apply in poorly immunogenic tumors. Genetic modification of tumor cells with anti-CD3 antibody has been proposed as an alternative therapeutic strategy. Transgene delivery, however, remains a challenge in vivo. Here, the authors genetically modified hepatocellular carcinoma (HCC) cells with a constructed membrane-bound anti-CD3scfv gene within the tumor site using the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) transgene system. They found that membrane-bound anti-CD3scfv activated lymphocytes, which lysed HCC cells bypassing the expression of antigens or MHC restriction. The findings highlight the approach as a promising strategy for solid tumor immunotherapy.

Whart's new?

While cancer immunotherapy with tumor-infiltrating lymphocytes is promising, the systemic application of high doses of interleukin-2 (IL-2) necessary for lymphocyte proliferation in solid tumors is often highly toxic. Here, the authors show that tumor-selective production of IL-2 from an oncolytic adenovirus successfully replaced the systemic application and improved the efficacy and safety of adoptive cell therapy in two complementary animal models. These results form the basis for a phase I clinical trial in melanoma patients.

What's new?

Increased expression of vascular endothelial growth factor (VEGF) is associated with a poor prognosis in patients with osteosarcoma. In this study, the authors asked whether the anti-VEGF drug bevacizumab might enhance standard chemotherapy and improve patient outcomes. Unfortunately, despite promising preclinical studies, the answer was no. The bevacizumab also increased the risk of serious wound-healing complications. The authors conclude that further evaluation of bevacizumab in osteosarcoma is therefore not warranted. However, the study provides important data regarding the use of antiangiogenic agents when surgical resection of a primary bone tumor is required.

What's new?

HER2 is overexpressed in many gastric cancers (GC). The anti-HER2 antibody trastuzumab has been a useful addition to standard chemotherapy in HER2-positive, metastatic GC. In this study, the authors linked trastuzumab with a light-reactive porphyrin to create a novel photoimmunoconjugate drug. When it was used for photodynamic therapy (PDT), this molecule showed promise both in vitro and in xenograft studies. But would it improve treatment results in human HER2+ GC patients? With repetitive cycles of Trast:Porph PDT, the answer appears to be “yes.”