Editors’ Selections from Relevant Scientific Publications

Physical activity delays PDAC development (by Pita-Grisanti et al via Cancer Research)A new study investigated the impact of physical activity on inflammation and the development of obesity-associated pancreatic ductal adenocarcinoma (PDAC). Using a genetically engineered mouse model with pancreatic-specific inducible KrasG12D expression, Pita-Grisanti and colleagues found that physical activity reduced weight gain, suppressed systemic inflammation, delayed tumor progression, and decreased proinflammatory signals in adipose tissue, particularly when diet-induced obesity was concurrent with KrasG12D expression. However, neither physical activity alone nor in combination with diet-induced weight loss or chemotherapy prevented tumor growth in orthotopic mouse models, regardless of obesity status. Additionally, the researchers observed decreased levels of proinflammatory cytokines and growth factors in 12 overweight or obese adults who participated in a 10-week voluntary running program. Overall, the findings suggest that physical activity reduces inflammation and induces signaling pathways to suppress pancreatic cancer, supporting the role of weight management strategies in reducing the risk of developing PDAC.Pita-Grisanti V, … Cruz-Monserrate Z. Cancer Res. 2024 Sep 16;84(18):3058–3071.Non-transformed Brca1−/−;Trp53−/− confetti clones (adapted from Fig. 1F by Ciwinska et al. via Nature)A new study may help explain why most oncogenic mutations in individual mammary stem cells (MaSCs) do not lead to tumors. Ciwinska and colleagues traced cell lineages in a “confetti” mouse model whose mammary glands contained a mixture of wild-type, Brca1−/− and Trp53−/− cells. They found that MaSCs were evenly distributed along the ducts and their descendant cells were short-lived, limiting the spread of mutations to a single MaSC-descendant unit. In addition, each estrous cycle remodeled the ducts’ anatomy, clearing out most self-renewing cells and eliminating most mutant clones, regardless of whether they carried oncogenic mutations. The ducts’ geometry further restricted clone expansion, providing an additional layer of protection against oncogenic mutations. However, during any given estrous cycle, clones that survived by chance could expand exponentially, potentially leading to the spread of mutant cells and increased susceptibility to transformation. These findings may help explain why breast cancer risk in humans increases with the number of menstrual cycles.Ciwinska M, … van Rheenen J. Nature. 2024 Sep;633(8028):198–206.A Waterpipe exhibited in the Vietnam Museum of Ethnology (by Daderot via Wikimedia Commons)A study in Vietnam shows that waterpipe smoking is associated with a higher risk of cancer mortality than cigarette smoking. Le and colleagues analyzed data from 39,401 participants in the Hanoi Prospective Cohort Study and found that individuals who smoked cigarettes, waterpipes, or both had an increased risk of dying from liver, lung, stomach, or nasopharyngeal cancers compared to never-smokers. Individuals who exclusively smoked waterpipes—especially those who smoked 11 to 15 times per day—had the greatest increase in risk, followed by those who used both smoking methods. The trend was most prominent in men, who represent the majority of smokers in Vietnam. The researchers call for stronger regulations on waterpipe usage in Vietnam and other countries where the practice is prevalent, including health warning labels, taxation, and age restrictions on purchasing waterpipe products.Le NT, … Luu HN. JAMA Oncol. 2024 Sep 1;10(9):1237–1244.Protocol to assess pulmonary nodules (adapted from Fig. 5E by Wang et al. via Nature Medicine)This study assessed the triage-driven Chinese Lung Nodules Reporting and Data System (C-Lung-RADS) to estimate the malignancy risk of lung nodules. Wang and colleagues analyzed data from 59,501 Chinese participants screened for lung cancer and collected information on nodule size and density. C-Lung-RADS identified 6, 10, and 18 mm as the cutoff values for the four risk types of solid nodules, and 6 and 20 mm as the cutoff values for low, mid, and high-risk pure ground glass nodules. C-Lung-RADS demonstrated a superior sensitivity compared with the previous system, Lung-RADS v2022 (87.1% vs. 63.3%). This artificial intelligence-enhanced approach may improve decision-making during screening and facilitate a faster and more efficient lung cancer diagnosis during routine checkups and targeted screening.Wang C, … Li W. Nat Med. 2024 Sep 17