Topical therapy for regression and melanoma prevention of congenital giant nevi
A mouse study shows that proinflammatory topical therapy can shrink giant nevi: large, pigmented areas of skin that can become cancerous. In humans, giant nevi can cover up to 80% of the body’s surface and progress to melanomas 12% of the time. Choi et al. developed a genetically modified mouse model of giant nevi that developed pigmented skin patches and melanoma. They then treated the pigmented areas with inhibitors of the signaling molecules MEK, PI3K and c-KIT, or squaric acid dibutylester (SADBE), a topical treatment that induces inflammation and recruits macrophages. These treatments cleared much of the pigmentation and SADBE treatment eliminated the risk of melanoma. SADBE was also effective at treating patches of human nevi that had been grafted onto mice, suggesting that topical therapies that induce this type of inflammation could be developed to treat children with congenital giant nevi.
β-Hydroxybutyrate suppresses colorectal cancer
This dietary screening study compared six different diets, including 2 ketogenic diets, in mice with colorectal cancer (CRC) induced by azoxymethane injection followed by 3 cycles of dextran sodium sulfate. Dimitieva-Posocco et al. found that ketogenic diets exhibit a strong tumor-inhibitory effect, which can be reproduced by the ketone body β-hydroxybutyrate (BHB). BHB reduces proliferation of colonic crypt cells and suppresses intestinal tumor growth via the surface receptor Hcar2 and the transcriptional regulator Hopx. These findings are supported by cancer organoid assays and RNA sequencing of biopsies from patients with CRC. This study identifies a BHB-triggered pathway regulating intestinal tumorigenesis and indicates that interventions with a single metabolite may complement prevention and treatment strategies for CRC.
Genome-wide mapping of somatic mutation rates uncovers drivers of cancer
A new kilobase-scale model of mutation rates across the tumor genome could reveal new cancer-driving mutations. As tumors grow, genomic elements that drive carcinogenesis mutate more frequently than others. Sherman et al. developed a probabilistic deep learning system, Dig, that identified driver mutations across the genomes of 37 different cancer types by calculating the mutation rates within a tumor. The researchers found driver mutations in surprising places throughout the genome, including genes that rarely mutate and non-coding regions such as intronic cryptic splice regions and 5′ untranslated regions. This model outperforms existing methods and is also 1-5 orders of magnitude faster. It provides a useful resource to discover putative cancer drivers.
Metagenomic Identification of Microbial Signatures Predicting Pancreatic Cancer From a Multinational Study
Certain ratios of bacterial species in the body can predict the occurrence of pancreatic ductal carcinomas (PDAC). Nagata et al. collected gut and oral microbiome samples from 47 Japanese PDAC patients and 235 controls. By analyzing the collection of microbial genomes in each sample, they found 30 gut species and 18 oral species whose prevalence was similar among the PDAC patients. To account for environmental conditions that could influence the microbiomes, the researchers then looked for these signatures in 107 people from Spain and 76 from Germany. They found similar associations; in particular, PDAC patients’ microbiomes contained more Streptococcus and Veillonella and less Faecalibacterium prausnitzii. Metagenomic analyses could provide a biomarker to help screen for pancreatic ductal carcinomas.
Absolute Risk of Oropharyngeal Cancer After an HPV16-E6 Serology Test and Potential Implications for Screening: Results From the Human Papillomavirus Cancer Cohort Consortium
Robbins et al. analyzed 365 subjects with oropharyngeal cancer (OPC) and 5,794 control subjects to construct a prediction model focused on determining the risk of developing OPC. The authors integrated the relative odds of OPC using seropositivity for human papillomavirus (HPV) 16-E6 oncoprotein, US population risk factor data, and US sex-specific population rates of OPC and mortality. The results of this study estimated that a substantial portion of the HPV16-E6 seropositive population will develop OPC with a 10-year risk of 17–27% for males and 4–6% for females aged 50–60. This study identifies a potential screening strategy to identify individuals at high risk of developing OPC who could benefit from monitoring with a minimally invasive test for HPV16-E6.
Age at Initiation of Lower Gastrointestinal Endoscopy and Colorectal Cancer Risk Among US Women
This prospective cohort study explored the association between endoscopy initiation at different ages and risk of colorectal cancer (CRC) among US women. The study utilized data from 111,801 women aged 26–46 years at enrollment, including 519 documented CRC cases. Ma et al. found that undergoing endoscopy before 45 years of age was associated with a significantly lower risk of incident CRC. The absolute reduction in estimated cumulative incidence of CRC through 60 years of age was 72 per 100,000 persons for initiation of endoscopy at 45–49 years vs 50–54 years of age. This study supports screening for CRC at 45 years of age and provides evidence for CRC screening in a younger population.
RSS Feeds