What's new?

Nevi, or moles, generally are considered benign, with the exception of nevi resulting from sun exposure, which are associated with increased risk of malignant melanoma. Recent evidence linking elevated nevus count to increased telomere length, however, suggests that nevus number also is a risk factor for internal cancer. In this study involving two prospective cohorts of U.S. women, overall internal cancer risk was higher among individuals with one or more nevi on the extremities compared to individuals without nevi. Increase in risk was dose dependent. Further investigations are needed to evaluate nevus count as a marker of cancer risk.

What's new?

Long-term survival to 15 years among germ cell testicular cancer survivors treated in the cisplatin era, marked by the introduction of cisplatin in the late 1970s, generally has been excellent. Beyond 20 years, however, survival rates decline. In this analysis of data on Norwegian men diagnosed with testicular cancer between 1980 and 2009, an increased overall risk for nongerm cell second cancer was detected among survivors, despite treatment. Risk was elevated in particular beyond 10 years of follow-up after cisplatin-based chemotherapy or radiotherapy. Despite reduced treatment intensity, two or more cycles of cisplatin-based chemotherapy was associated with continuing increased second cancer risk.

What's new?

While menopausal hormone therapy (MHT) appears to influence ovarian cancer risk, whether the risk varies between various MHT treatment options remains unknown. In this Swedish population-based matched-cohort study, including all MHT receivers during 2005–2012, we found notable differences between MHT regimens. In addition, cutaneous EP-MHT suggested for less risk than the most commonly prescribed oral MHT. These findings are important for choosing a MHT treatment option, which involves less excess ovarian cancer risk.

What's new?

Consumption of processed meat has been associated with non-cardia gastric cancer, but evidence regarding a possible role of red meat is more limited. Here, the authors explore associations between white, red, and processed meat consumption and gastric cancer risk through an individual participant data meta-analysis of case-control studies within the Stomach cancer Pooling Project. An increased risk of gastric cancer was observed with high intakes of red and processed meat, with further confirmation through the computational and graphical depiction of the exposure-response associations. Adherence to dietary recommendations to reduce meat consumption may contribute to reducing the burden of gastric cancer.

What's new?

Interactions between tobacco smoking and human papillomavirus (HPV) infection potentially result in supra-additive effects on head and neck cancer (HNC) risk. The level of risk may be modified, however, by the timing of exposure to these factors over an individual's life course. Here, in a study population that included ever-smokers and HNC patients, retrospective life course smoking trajectories among HPV-positive HNC cases and controls were similar. Tobacco smoking even four decades prior to diagnosis was associated with elevated HNC risk, regardless of HPV status. HNC risk was increased particularly for HPV-positive study participants who smoked before becoming sexually active.

What's new?

Higher birthweight is associated with increased risk of breast cancer, especially in premenopausal women. In this study, the authors analyzed the effect of adult weight and height on the association between birthweight and postmenopausal breast cancer. They enrolled 70,397 postmenopausal women and monitored their breast cancer incidence over a 25-year follow up. Women under 6 pounds at birth had reduced cancer risk, but more than 40% of this effect was mediated by adult height. High birthweight was not associated with postmenopausal breast cancer risk. Adult weight gain was associated with increased risk, regardless of birthweight.

What's new?

Some evidence has suggested an increase in cancer associated with total hip arthroplasty, but prior studies have been inconclusive. For this study, the authors recruited 126,276 patients who had received cemented THA and 555,575 age- and sex-matched controls. They limited patients to those whose THA was due to primary osteoarthritis, which generated a relatively homogenous patient population in terms of age and general health. The patients were recruited from the Swedish national THA registry, and cancer incidence was compared between the two groups. They found no increase in cancer risk associated with total hip arthroplasty.

What's new?

Although chronic inflammation likely influences prostate cancer development, a clear association is yet to be established. In particular, uncertainties remain regarding the relationship between systemic inflammatory markers and prostate cancer. In this investigation of data for more than 7,350 men, pre-diagnostic levels of C-reactive protein (CRP), measured via high-sensitivity CRP (hs-CRP) testing at study entry and at follow-up, were associated with a dose-response increase in prostate cancer risk. Risk and disease severity were further associated with a combined score incorporating both hs-CRP and white blood cell count, highlighting the relevance of inflammation in prostate cancer development and prognosis.

What's new?

Gastroesophageal reflux disease (GERD), a risk factor for esophageal adenocarcinoma (EAC), affects substantial proportions of some Western populations. GERD complications, including invasive EAC, are detectable by endoscopy, though whether endoscopy benefits EAC survival is unknown. Here, EAC patients with history of GERD had improved survival over EAC patients with no history of the condition. Prognosis, however, was similar between patients with and without previous screening endoscopy. Moreover, although endoscopy frequently is indicated in GERD, most patients studied had no previous GERD diagnosis and had not undergone endoscopy prior to EAC diagnosis, indicating a need to re-evaluate EAC screening strategies.

What's new?

These days, more children and adolescents who develop central nervous system tumors are surviving to adulthood. For these patients, it's important to understand the effect their disease and the treatment will have on their reproductive life. Here, the authors investigated the risk of preterm birth among children of CNS tumor survivors. They found an increased risk of preterm birth for babies born to people diagnosed with CNS tumors as children, but not adolescents. The increase in risk was particularly evident in survivors of medulloblastoma or ependymoma. However, the risk diminished gradually over time, suggesting the damage may heal.

What's new?

While head and neck squamous cell carcinoma that are caused by human papillomavirus can be treated relatively well, virus-negative tumors have a poor prognosis. In this large multi-institutional study, the authors found that cisplatin- and carboplatin-based regimens—in concurrent chemoradiotherapy—were superior to antibody-based therapies, with carboplatin-based regimens representing a more tolerable alternative for patients with virus-negative tumors.

What's new?

The programmed cell death-1 protein receptor (PD-1) and its ligand (PD-L1) checkpoint pathway play a critical role in promoting tumour growth. However, whether PD-L1-positive patients derive more overall survival benefit from PD-1/PD-L1 inhibitors in the treatment of advanced solid tumours remains unclear and inconclusive. The present meta-analysis demonstrated that PD-1/PD-L1 inhibitors significantly improved overall survival in both PD-L1-positive and negative patients compared with controls, but the magnitude of the benefit was clinically PD-L1-dependent. The evidence suggests that both future research in anti-PD-1/PD-L1 therapies and clinical practice should take into account PD-L1-related heterogeneity of responsiveness to treatments.

What's new?

In Africa, the continent with the highest burden of cervical cancer globally, nearly three quarters of cases occur in rural areas. Per the World Health Organization, HPV-based screen-and-treat is a preferred strategy for cervical cancer secondary prevention in limited resource settings. However, the successful implementation of this recommendation in rural and remote areas of Africa remains uncertain. Here, the authors designed and piloted a culturally appropriate screening strategy with self-collected HPV testing, and found that community engagement is critical to achieve success. In particular, education on the proper sampling procedure and follow-up of women who are HPV positive are essential.

What's new?

Cancer cells fuel their rapid growth by shifting energy metabolism pathways to aerobic glycolysis, thereby enabling accelerated production of ATP, the energy currency of cells. The pyruvate kinase isoform M2 (PKM2) plays a critical role in catalyzing pyruvate and ATP generation in the final step of glycolysis. This study shows that PKM2 is highly expressed in melanoma and that its activity is correlated with melanoma cell invasion and migration. PKM2 activity was successfully inhibited by the decarboxylase inhibitor benserazide, both in vitro and in vivo. In the process of blocking glycolysis, benserazide also facilitated a return to normal energy metabolism.

What's new?

Current breast cancer treatment guidelines recommend that chemotherapy is initiated between 6-12 weeks after surgery. Delayed treatment can lead to poorer outcome, but there's no precise definition of the optimal window. Recent work suggests that for patients with triple negative breast cancer (TNBC), it's best to initiate chemotherapy within 30 days. Here, the authors evaluated outcomes for TNBC patients correlated with time to chemotherapy. They found that in patients undergoing breast-conserving surgery, an interval of more than 30 days before chemotherapy was associated with decreased survival. If the patient had undergone a mastectomy, a longer delay before chemotherapy did not impact survival.

What's new?

Dose-dense chemotherapy is standard of care in high-risk early breast cancer; however, its role in HER2-positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we showed that the benefit of dose-dense chemotherapy appeared to be small (if any) in HER2-positive patients who received trastuzumab raising concerns on the need of chemotherapy escalation approaches in this setting. These findings may guide the choice of adjuvant chemotherapy in HER2-positive early breast cancer patients.

What's new?

A large number of long noncoding RNAs (lncRNAs) have been shown to regulate tumor proliferation and progression in various cancers. However, the role of lncRNAs in pancreatic cancer remains to be fully elucidated. Here, the authors demonstrate that lncRNA SOX2OT can promote the proliferation of pancreatic cancer cells via direct interaction with the RNA-binding protein FUS. SOX2OT bonding affects the protein stability of FUS, with FUS subsequently supporting proliferation by regulating cell cycle-associated factors CCND1 and p27. The results reveal the involvement of the SOX2OT-FUS-CCND1/p27 axis in pancreatic tumorigenesis, which may help develop new approaches for human pancreatic cancer therapy.

What's new?

Noncoding regulatory mutations on the core promoter of human telomerase reverse transcriptase (hTERT) have been shown to affect gene expression in cancer. Using a protein microarray of 667 transcription factor DNA-binding domains and subsequent functional assays, the authors identified an ETS transcription factor family member – FLI1 – that binds preferentially to mutated, cancer-associated hTERT promoters, thereby modulating cell cycle progression through regulation of the G1/S transition. FLI1 could exert both oncogenic and tumor suppressive roles in a tissue-specific manner. Taken together, the data indicate a cell cycle regulatory hub involving FLI1, hTERT, CCND1, and E2F2 in a tissue- and context-dependent manner.

What's new?

The adenosinergic system plays an important role in the development of many types of cancer. However, the underlying mechanisms remain poorly understood. This study set to identify the oncogenic function of the adenosine receptor 2B (ADORA2B) in head and neck squamous cell carcinoma (HNSCC)-derived tumor cells. The results show that ADORA2B is upregulated and constitutively active in HNSCC-derived cell lines. This activity is sufficient to promote autonomous cell growth, migration, and angiogenesis in vitro and in vivo. The data suggest ADORA2B as an important biomarker and potential therapeutic target for the treatment of HNSCC and other ADORA2B-expressing solid tumors.

What's new?

Head and neck squamous cell carcinoma (HNSCC) recurs in more than half of patients, with most ultimately dying from metastatic disease. In order to reverse this trend, a better understanding of molecular alterations that contribute to HNSCC is needed. Here, the authors identify a link between G-protein-coupled receptor kinase 2 (GRK2), a key signaling hub, and HNSCC, whereby high-grade HNSCC tumors were found to exhibit atypically low GRK2 levels. Experiments in HNSCC cells further revealed that GRK2 silencing triggers epithelial-to-mesenchymal transition features, suggesting that GRK2 serves a key role in preserving the differentiated epithelial phenotype of squamous cells.

What's new?

Triple-negative breast cancer (TNBC) has a high degree of molecular diversity, with multiple subtypes and varying metastatic behavior. To better understand TNBC heterogeneity, the authors of this study performed RNA expression analysis on four isogenic MDA-MB-231 human TNBC tumour models characterized by distinct metastatic capacities. The three metastatic variants upregulation of the fibroblast growth factor FGF13. Elevated FGF13 expression was associated with poor survival in patients with basal-like breast cancer. In mice, FGF13 knockdown in highly metastatic MDA-MB-231 cells reduced spontaneous metastasis to liver and lung without affecting primary xenograft growth, suggesting that FGF13 is a promising antimetastatic target.

What's new?

To date, little is known on the processes linking cerebrovascular inflammation and the formation of brain metastases. Moreover, while the vascular cell adhesion molecule-1 (VCAM-1) is known to promote transendothelial migration of cancer cells to different organs, it is unclear whether a similar mechanism occurs within the specialized environment of the brain. Using histological analyses and MRI images detecting VCAM-1-targeted microparticles of iron oxide in a brain inflammation mouse model, here the authors show that an increased level of VCAM-1 expression contributes to the enhanced formation of brain metastases. Blocking VCAM-1 reduces the metastatic burden down to control values.

What's new?

Intraoperative frozen section (IFS) analysis is used in clear cell renal cell carcinoma (ccRCC) to confirm diagnosis during partial nephrectomy. Surgical margin evaluation using IFS analysis is time-consuming and unreliable, however, leading to relatively low utilization. Here, the authors evaluated the feasibility of using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) in assessing ccRCC in core tissues. Their combined predictive model consisting of differentially expressed metabolites and the ratio of glucose to arachidonic acid could discriminate cancer vs. normal tissue with an accuracy of 85%. DESI-MSI thus demonstrates promise as a method to improve detection of positive surgical margins intraoperatively.

What's new

Tumor cells can interact with the surrounding microenvironment, to alter gene expression, suppress immune function, and enhance their own growth. While trastuzumab has dramatically improved clinical outcomes for patients with HER2-positive breast cancer, not all tumors respond to treatment. In this study, the authors found that one mechanism of trastuzumab resistance may be due to altered gene expression representing “reactive” stromal cells surrounding the tumor, even when high levels of tumor-infiltrating lymphocytes (TILs) are present. These “reactive” genetic signatures may provide valuable biomarkers for predicting treatment response.

What's new?

To date, there are no reliable markers to identify endometrial cancer patients with worse outcomes who may benefit from adjuvant treatments. Peritoneal lavages are systematically performed during endometrial surgery, but little data is available about their potential as liquid biopsies. In this proof-of-concept study, the authors demonstrated that circulating-free DNA can be purified from peritoneal lavages of surgically-resected endometrial cancer patients. Hotspot somatic mutations were detected in a significant percentage of cases and matched tumor tissue mutations. The results warrant further studies to determine if mutation testing of liquid biopsies may help to identify endometrial cancer patients with worse prognosis.

What's new?

Some reports suggest short overall survival (OS) and chemoresistance of mismatch repair-deficient and/or microsatellite instability-high metastatic colorectal cancers (dMMR/MSI mCRC). In a large multicenter series of dMMR/MSI mCRC we observed a relatively long OS but short progression-free survival. Irinotecan-based chemotherapy was not associated with better OS than oxaliplatin-based chemotherapy but anti-VEGF, as compared to anti-EGFR, was associated with a trend to longer OS. These results could help clinicians to choose treatment in patients with dMMR/MSI mCRC.