What's new?

Breast-cancer risks differ between women of African ancestry and women of European ancestry, especially for aggressive, hormone-negative tumors. In this large African study, the authors found that, while increased parity reduced the risk of all breast-cancer subtypes after age 50, the opposite was true for risk of developing estrogen-receptor (ER) negative tumors at a younger age. However, longer breastfeeding appeared to reduce the risk both for early-onset, ER-negative tumors and for all tumor subtypes with later onset. Efforts to promote extended breastfeeding may thus help reduce many breast cancers in this population.

What's new?

Certain cancer types that originate from the epithelial or mesothelial tissues of the thoracic cavity are exceedingly rare. As a consequence, little is known about their incidence and survival. Here, utilizing national databases, the authors estimated incidence and survival of malignant mesothelioma (MM) and other rare thoracic cancers in Germany and the United States. Analyses show that between 2000 and 2014, MM incidence declined in both countries, although only MM survival improved in Germany. No improvements were observed in either country for survival of epithelial tumors of the trachea and thymus, highlighting a need for preventive and therapeutic advances.

What's new?

Ketone bodies and medium-chain fatty acids may be used as a tool to induce cancer cells to switch between glycolysis and oxidative phosphorylation in cellular respiration, which, therefore, may have an effect on treatment response and outcomes of cancer patients. In the present study, we investigated the role of genetic variants in ketone-related pathway genes in survival of lung cancer patients and found that three genetic variants located in PLIN2, SULT2A1 and UGT1A9, respectively, were independently associated with survival of patients with non-small cell lung cancer. The survival-associated variant in PLIN2 was also associated with mRNA expression levels in lymphoblastoid cells and thus may serve as a potential biomarker for lung cancer survival.

What's new?

Magnesium is believed to be involved in cancer pathogenesis, with magnesium intake reducing the risk for a variety of cancers. Epidemiological studies on magnesium intake and primary liver cancer (PLC) remain scarce, however. Using prospective data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, here the authors found that total (diet + supplements) and dietary magnesium intakes were inversely associated with risks of PLC incidence and mortality in a non-linear dose–response manner. These findings suggest that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality in the US population.

What's new?

Increasing evidence supports a positive association between periodontal disease and total cancer risk. Here, for the first time, the authors studied the association between periodontal disease, edentulism, and total cancer mortality by using a standardized clinical dental examination in a U.S. nationally representative population and adjusting for social and shared risk factors for cancer and periodontal disease. Participants with edentulism, but not periodontal disease, had a higher risk of cancer death even after taking into account demographics, shared risk factors, and social factors. This study supports the growing literature on the importance of dental health for cancer prevention and control.

What's new?

Adipokines and C-reactive protein have been linked to breast cancer risk in observational studies. But while these molecular mediators potentially connect excess adiposity with breast cancer, whether the associations are causal in nature is uncertain. Here, a Mendelian randomization approach was employed to estimate the causal effect of six circulating adipokines and C-reactive protein on breast cancer risk. Overall, among 122,977 cases and 105,974 controls, analyses provided little evidence supporting a causal role for these molecular markers in breast cancer etiology. The findings warrant investigation of other mediators that could explain apparent links between adiposity and increased breast cancer risk.

What's new?

The incidence of testicular cancer (TC) has increased substantially in many countries, with the highest incidence found in Denmark and Norway. The reasons remain unknown, however. This population-based study found a clear difference in TC incidence among individuals born in Norway and descendants of Scandinavian people born in Utah. Norwegian males born between 1980 and 1984 had twice the TC incidence found in Utah in the same period. These differences in TC rates point to the possibility of environmental influences and/or lifestyle factors. A family history of TC was a strong risk factor for developing testicular cancer in both populations.

What's new?

Now that testing for high-risk human papilloma virus (HPV) types is being adopted globally for cervical cancer screening, instructions on how to manage the many patterns of HPV positivity/negativity over multiple screening rounds are needed. The authors analyzed results from 15 years of screening at Kaiser Permanente Northern California including a million women. They analyze incidence rates and proportion of precancerous, CIN3+ lesions and corroborate previous findings that most CIN3+ lesions are found at the first positive test.

What's new?

This is the first large study to investigate the effect of high consumption of mustard oil and its differential effects when fresh fish is cooked by deep-frying compared to shallow-frying. In this study, the authors found that high consumption of mustard oil probably contaminated and the practice of deep frying in mustard oil was associated with an increased risk of GBC. These results have important implications for public health measures to reduce GBS risk, as well as suggesting further studies on the molecular mechanisms involved.

What's new?

Mozambique established a national cancer registry in 2016. Two regional registries are operational: one in the capital city of Maputo, and the other in Beira. These authors report on the first analysis of data collected in these registries, between 2014 and 2017. Overall, they report, 44% of cancers in Maputo and 52% in Beira appear to result from infectious agents, particularly HIV. They also compared the current data with cancer incidence measured in 1956–60, and found that incidence of breast, prostate, and colon are on the rise. These data provide important guidance for establishing priorities within the National Cancer Control Plan.

What's new?

Although marked declines have been observed in incidence worldwide, cervical cancer continues to disproportionally affect women in Latin America and the Caribbean. Here, the authors present the most up-to-date data on the cervical cancer burden in 32 countries/territories in the region. In 2018, there were an estimated 56,000 and 28,000 new cervical cancer cases and deaths, respectively, with great variations between countries/territories. Despite a recent decrease in cervical cancer incidence and mortality, rates remain high. Thus, achieving the elimination of cervical cancer in the region still requires substantial political commitment and economic effort, including the establishment of population-based cancer registries.

What's new?

The transmembrane CD146 glycoprotein is expressed by a variety of cancer cell types and is correlated with poor cancer prognosis and tumor aggressiveness. Its expression further is associated with epithelial-to-mesenchymal transition (EMT) and tumor metastasis. Here, soluble CD146, shed from membrane-anchored CD146, was found to be highly secreted by CD146-positive tumors and to induce EMT, cancer stem cell generation, and tissue factor expression in cancer cells. These effects were blocked by M2J-1 mAb, a novel antisoluble CD146 antibody. M2J-1 mAb could thus constitute a new therapeutic option to prevent tumor dissemination and procoagulant activity in many invasive CD146-positive cancers.

What's new?

Ponatinib is a small-molecule multi-tyrosine kinase inhibitor clinically approved for anticancer therapy. However, to date, the intracellular pharmacokinetics of this compound and the molecular mechanisms underlying resistance in cancer cells remain largely unknown. Here, the authors found that ponatinib was selectively scavenged by lipid droplets in cancer cells. Ponatinib accumulation into lipid droplets emerged as a critical determinant of intrinsic and acquired drug resistance. The findings suggest that lipid droplets represent an underestimated organelle influencing intracellular pharmacokinetics and anticancer tyrosine kinase inhibitor activity. Moreover, co-targeting of lipogenic cancer cell phenotypes might enhance the efficacy of ponatinib and other lipophilic pharmaceuticals.

What's new?

Stem cell-derived extracellular vesicles (EVs) can reprogram target cells and promote tissue repair by transferring their cargo. However, the anti-tumor activity of EVs derived from different stem cell sources has been investigated with conflicting results. Here, the authors demonstrate for the first time the anti-tumor effect of EVs from human liver stem cells (HLSC-EVs) in a systemic intravenous administration model. HLSC-EVs had a selective effect on cancer stem cells that could be ascribed to the transfer and induction of anti-tumor miRNAs. This study highlights the potential clinical use of stem cell-derived EVs, alone or in combination with other cancer therapies.

What's new?

Hypo-fractionated radiotherapy may enhance anti-PD-1 antibody efficacy, but the findings remain controversial. In this study of 26 consecutive melanoma patients who failed anti-PD-1 monotherapy, hypo-fractionated radiotherapy combined with an unmodified anti-PD-1 monoclonal antibody regimen was well tolerated and induced long-lasting responses, with confirmed complete and partial responses in 10 patients. Progression-free survival curves achieved a plateau. Anti-PD-1 regimen was interrupted in 9 patients achieving response, with only 1 relapse observed after 10 months. This study proposes a new therapeutic strategy after failure of anti-PD-1 therapy to rescue patients with metastatic melanoma who have a fairly poor range of treatment options.

What's new?

Epithelial-mesenchymal transition (EMT) is an essential prerequisite for metastatic spread and resistance against chemotherapy, which cause major clinical problems in colorectal and other carcinomas. CRK adaptor proteins are known as downstream effectors of SRC/FAK kinases. Here, the authors demonstrate that CRK proteins mediate the EMT-associated phenotypes of colorectal cancer aggressiveness, act as novel feedback amplifiers of SRC/FAK kinase signaling, and induce c-MYC signaling. The findings highlight CRK family adaptor proteins as promising therapeutic targets to counteract EMT, chemoresistance, metastasis formation, and minimal residual disease. Moreover, as proof of concept, CRK family-mediated oncogenic signaling was successfully inhibited by a peptide-based inhibitor.

What's new?

In ovarian cancer, numerous tumor suppressor genes have been shown to be silenced by promoter hypermethylation and associated with disease features. However, few studies have examined concurrent methylation of multiple genes. Harnessing cell-free DNA as a promising minimally-invasive tool, here the authors report the development of a biomarker panel for the simultaneous detection of promoter methylation of HOXA9 and HIC1 suppressor genes in a blood-based assay. The panel achieved enhanced sensitivity and specificity in distinguishing individuals with ovarian cancer from controls. Overall, the study provides a proof of principle that serum DNA methylation markers could help detect early ovarian cancer.