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In Australia, 62% of adults are overweight or obese and 48% are insufficiently physically active. Many cancer types are believed to be causally associated with overweight/obesity or prevented by physical activity. This study estimates the proportion of avoidable cancers under different theoretical intervention scenarios to reduce the prevalence of overweight/obesity and physical inactivity. Up to 12% of overweight/obesity-related cancers (~190,000 cancers) and up to 2% of inactivity-related cancers (~19,000 cancers) could be avoided in Australia over the next 25 years. This study provides policy-relevant information on the magnitude of cancer prevention achievable through interventions and how long it would take.

What's new?

Fermented dairy foods, owing to their rich nutrient and probiotic content, are associated with a wide range of health benefits. Whether those benefits include a reduction in cancer risk is unknown. In the present meta-analysis, which included 61 studies with more than 1.9 million participants and more than 38,000 cancer cases, statistical evidence supported an association between fermented dairy food intake and an overall decrease in cancer risk. Associations varied, however, for specific cancer types. In particular, yogurt consumption was linked to decreased bladder cancer and colorectal cancer risk but increased prostate cancer and renal cancer risk.

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Colorectal carcinoma (CRC) is on the rise in China due to a westernized lifestyle but a thorough molecular characterization of these tumors is lacking. Here the authors determined mutation rates of KRAS and BRAF, two critical growth-control factors, in a large study of CRC patients in China. Both mutations occurred more frequently in female patients with right-sided CRCs but significantly differed in their differentiation state, underscoring the need for comprehensive molecular diagnostics in the management of CRC patients in China.

This is the first Europe-wide study (37 cancer registries, 9 countries) analysing the effect of comorbidities on whether women with early breast cancer (diagnosed 2009–13) receive standard treatments. Women with no comorbidities usually received standard treatments, but elderly women often received less prompt and non-standard treatments, irrespective of comorbidities, with increased probability of relapse and mortality. All women, particularly the elderly, should receive standard treatments wherever possible to maximize the benefits of modern evidence-based approaches.

What's new?

While overweight and obesity are known risk factors for cancer, the impact of these conditions at midlife on the development of site-specific cancers after age 65 is uncertain. Here, in a Swedish twin cohort, overweight at ages 30 to 50 was associated with an increased risk of developing colon, liver, or uterine cancer after age 65. Overweight at midlife was also linked, however, to a significant decrease in non-melanoma skin cancer risk in late life when compared to normal weight individuals. Understanding the degree to which genetic and early-life environmental factors contribute to these associations requires further investigation.

What's new?

While lifestyle and dietary factors are associated with colorectal cancer risk, most studies have examined associations only for individual factors. The influence of combinations of factors on colorectal carcinogenesis remains uncertain. Here, the authors created a healthy lifestyle score based on five dietary and lifestyle factors combined: non-smoking, low alcohol intake, healthy diet, adequate physical activity, and healthy weight. In analyses of health data and colonoscopy findings for screening colonoscopy participants in Saarland, Germany, healthy lifestyle score was inversely associated with risk of colorectal neoplasms. The findings indicate that healthy lifestyle pattern lowers risk of all stages of colorectal carcinogenesis.

What's new?

Why is cervical cancer on the rise in Japan, while it's decreasing in most other developed countries? These authors analyzed incidence rates in Japan and compared them with data from Japanese-Americans and South Korean women. They found increasing incidence among recent birth cohorts in Japan, which were not seen among Japanese-American or South Korean women. For one thing, cervical cancer screening uptake in Japan lags significantly behind that of South Korea and the US, reaching only 34% coverage in 2014. The strong birth cohort effect suggests an increasing prevalence of HPV, which can be counteracted by better screening and vaccination.

What's new?

Diet is the primary source of cadmium – a proven Group 1 human carcinogen – for non-smokers. Observational studies investigating the effect of cadmium from food sources on breast cancer risk have produced inconsistent results, however. This first cohort study to investigate the effects of dietary cadmium on the risk of breast cancer and breast cancer subtypes defined by the expression of ER, PR, and HER2 provides further evidence that dietary cadmium increases breast cancer risk. The lack of significant heterogeneity in risk estimates between different ER and PR status neither supports nor refutes the hypothesis that cadmium acts as a metalloestrogen.

What's new?

The prevalence of Lynch syndrome (LS) varies significantly in different ethnic populations. In this study, the authors screened more than 3000 Chinese colorectal cancer patients for mutations associated with LS, including mismatch repair (MMR) and BRAF^V600E mutations. They found that, while the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of mutations is different, including many not previously reported. Older patients had a decreased risk of LS, suggesting that germline sequencing may not be necessary in this population.

What's new?

Ago2-associated miRNAs can either be released by cytolysis or actively booted out of the cell. In our study, the authors showed which Ago2-complexed miRNAs are released by the different mechanisms. Because viable cancer cells release Ago-miRNA-21, it could serve as a biomarker to indicate the presence of cancer. Here, the authors used Ago-miRNA-21 to detect the presence of colorectal cancer. Conversely, Ago2-miR-200c appears in the bloodstream after cytolysis, and may indicate how well chemotherapy is killing tumor cells. The relationship between the two miRNAs could provide a window into tumor dynamics during treatment.

What's new?

Increasing Native American ancestry proportions are associated with decreasing breast cancer (BC) risk. This paper examines the contributions of genetic ancestry, established risk factors, and newly identified susceptibility variants to BC risk in a Colombian population with diverse proportions of European, Native American, and African ancestry. The authors demonstrate that individual ancestry proportions predict breast cancer risk in Colombia as accurately as established breast cancer risk factors. They also develop a multifactorial risk score and examine its potential for breast cancer risk prediction. The findings underline the relevance of considering genetic ancestry in the breast cancer care of Hispanic populations.

What's new?

Genetic and environmental risk factors for ovarian cancer have been identified separately but interactions between both remain largely unexplored. The authors identified a new gene x environment interaction between oral contraceptive pill (OCP) use and a single nucleotide polymorphism in the PVT1 gene, a long-noncoding RNA located on chromosome 8. The data suggest that the protective benefit of OCP use may be strongest in women with the T allele of PVT1 underscoring the need to tailor prevention strategies to individual genotypic profiles.

What's new?

Cervical cancer is driven by persistent infection of human papillomavirus (HPV), which is influenced by HPV type and intratypic variants. The impact of HPV type and intratypic variants on cervical cancer outcome remains poorly understood, however. The current study provides novel evidence that intratypic HPV variants play an important role in cervical cancer risk and disease outcome. Specifically, differences in viral type, HPV 16 lineage, and sequence variants within the E6 binding motif of HPV 16 significantly associate with survival of cervical cancer patients. These findings may drive the development of better prognostic markers and novel therapeutics for cervical cancer.

What's new?

While ovarian epithelial carcinoma is a leading cause of cancer death in women, little is known about its etiology. Here, anoctamin-1 (ANO1) proteins, which function as voltage-sensitive calcium-activated chloride channels, were found to be overexpressed in human epithelial ovarian cancer cells and tissues. In preoperative patients with ovarian tumors, ANO1 gene overexpression was detected in peripheral blood mononuclear cells. Meanwhile, ANO1 silencing in epithelial ovarian cancer cell lines inhibited proliferation and invasion and, in xenografts, suppressed subcutaneous tumor growth. ANO1 expression is a promising prognostic and diagnostic biomarker for epithelial ovarian cancer, and its inhibition therapeutically relevant for the disease.

What's new?

Despite the presence of rich vascular supply, anti-angiogenesis therapy has low efficacy in non-small cell lung cancers (NSCLCs). Vasculogenic mimicry (VM), the formation of vascular networks composed of aggressive cancer cells, may be one of the reasons. our study explored the effects of sema4D and its downstream RhoA/ROCK signaling pathway, which play an instrumental role in tumor angiogenesis, on tumor VM. Sema4D overexpression and consequential activation of the RhoA/ROCK pathway were linked with tumor cell plasticity and VM formation in NSCLC. Targeting both angiogenesis and vasculogenic mimicry through blocking sema4D and RhoA/ROCK signaling pathway may provide an alternative cancer treatment.

What's new?

Telomere dysfunction involving luminal progenitor cells in the mammary gland likely influences breast cancer development. The effects of telomere damage on mammary progenitor cells, however, are not fully known. Here, in a novel mouse model, depleted expression of telomeric repeat factor 2 (TRF2), characteristically reduced in human breast tumors, was associated with increased p53-dependent telomere DNA damage response and glandular fibrosis in mammary gland epithelium. In mammary stem cells, TRF2 deficiency further induced telomere shortening and genomic instability, which correlated with increased tumor proliferation. The findings shed light on mechanisms underlying mammographic density and telomere dysfunction in breast cancer.

What's new?

Circulating tumor cells (CTCs) hold promise as a liquid biopsy and model to study tumor biology. However, technical limitations toward CTCs molecular characterisation and ex vivo expansion remain. This work describes for the first time the development of a CTCs-derived xenograft (CDX) from a metastatic Triple Negative Breast Cancer (TNBC) patient, with WNT signalling emerging as the main tumor mechanism. Potential prognostic markers and therapeutic targets were further identified in CTCs from TNBC patients. This study demonstrates that CTCs from TNBC are tumorigenic and highlights CDXs as a unique tool to better understand TNBC biology and develop novel therapeutic approaches.

What's new?

Anaplastic thyroid cancer (ATC) is a rare malignancy that is notoriously aggressive. Fatality from ATC remains high, despite advances in multimodal therapy. Here, the authors investigated combination therapy employing tyrosine kinase inhibitors and checkpoint inhibitors as a novel treatment strategy in ATC. In a mouse model of orthotopic ATC, combined treatment with the tyrosine kinase inhibitor lenvatinib and an anti-PD-1/PD-L1 checkpoint inhibitor was found to dramatically reduce tumor volume and improve survival. While lenvatinib monotherapy was associated with increased tumor-infiltrating and circulating myeloid-derived suppressor cells (MDSCs), the depletion of MDSCs via combination therapy significantly augmented lenvatinib's effectiveness.

What's new?

Whether defects in bone marrow-derived mesenchymal stromal cells (MSCs) or aberrations in their interplay with hematopoietic stem cells contribute to acute myeloid leukemia (AML) is unclear. In this study, for seven AML patients, an ex-vivo system was developed using each patient's own stroma (POS) to replicate the bone marrow microenvironment. POS preferentially supported growth and aberrant cytokine expression in the same patient's AML cells. In addition, AML MSCs differed in shape and function compared to healthy MSCs and, in vitro, grew at significantly slower rates. The findings highlight a potential role for dysfunctional stroma in AML development and maintenance.

What's new?

The current dogma that tumor cells express sialic acids to dampen anti-tumor immunity has led to the development of novel therapeutic strategies aimed at dismantling sialic acid-induced tolerance. Yet the effect of a complete loss of tumor sialylation remains to be elucidated. This study is the first to report a detrimental effect of complete tumor desialylation on colorectal cancer tumor growth, which could be attributed to augmented CD8⁺ T cell apoptosis. The work revisits how tumor-associated sialic acids influence the anti-tumor immune response and has implications for the design of novel cancer therapeutics aimed at altering the tumor glycosylation profile.

What's new?

Tumor mutational burden (TMB) is an emerging biomarker to predict response to immune checkpoint inhibitors. While TMB can be measured by whole exome sequencing (WES), costs, turn-around time, and tissue availability currently favor a panel sequencing approach using FFPE tissue for routine diagnostics. However, performance remains to be clarified. Our study is the first worldwide that analyses three major commercial gene panels by comparing TMB approximation across panels as well as against the technical reference standard WES. The data suggest that TMB approximation using gene panel sequencing of FFPE tumor tissue is feasible and can be implemented in routine diagnostics.

Maintenance of circulating Epstein-Barr virus (EBV) DNA after treatment is associated with poor disease outcome in patients with nasopharyngeal carcinoma. Here the authors focused on the small percentage of patients who initially maintain EBV DNA after therapy but eventually clear this marker from their blood. These patients maintain a high risk of disease failure when compared to patients with no detectable post-therapy EBV DNA, underscoring the prognostic value of nuanced EBV DNA measurements after nasopharyngeal cancer treatment.

What's new?

One key theory for how tumor stroma facilitates tumor progression is the production of stroma factors influencing tumor metabolism. Here, the authors tested associations between markers of tumor metabolism and stroma infiltrate in colorectal cancer, which has tumor cell anaerobic metabolism as a prognostic factor. The combination of stromal infiltrate and tumor cell expression of nuclear LDH-5 was significantly associated with survival, increased tumor budding, and decreased stromal T-lymphocytes. The findings support the hypothesis that increased stromal invasion promotes tumor progression via modulation of tumor metabolism and highlights LDH-5 as a promising therapeutic target for patients with stromal-rich colorectal cancer.

What's new?

The viral oncogenes E6 and E7 of human papillomaviruses (HPVs) play a central role in cervical carcinogenesis caused by HPV infection. Whether they also mediate resistance against chemotherapeutic agents remains unclear. In this study, experiments in cervical cancer cells show that E6 counteracts cisplatin-induced cytotoxicity and increases drug-resistant variants. Suppression of E6 expression by an inhibitor of the bromodomain protein Brd4 enhanced chemoresponse when the inhibitor was co-delivered with cisplatin. The findings indicate that Brd4 inhibitors can improve cisplatin responses in cervical cancer, potentially allowing for reductions in cisplatin dose and associated reductions in side effects in patients.

What's new?

The management of HPV-positive women in the second HPV-based screening round may be different from the management in the first round. We showed that HPV-positive women in the second HPV-based screening round can be suitably managed by cytology, HPV16/18 genotyping and the HPV result at the previous screen, obviating the need for repeat testing of HPV-positive, cytology negative women.

What's new?

Genetic variants in the dihydropyrimidine dehydrogenase gene (DPYD) enhance toxicity associated with fluoropyrimidine-based chemotherapies and a 50% reduction in drug dosing in affected carriers. Here the authors addressed the fear of “underdosing” by retrospectively matching cancer patients with mutant or wild-type DPYD status. No significant difference was seen in overall survival, progression-free survival or disease control between the two groups affirming current clinical guidelines.