Latest Research
All publications from the Cancer3.AI database, newest first.
Identification and validation of natural product-based KRASG12D inhibitors through structure-based virtual screening, molecular dynamics simulation, and in vitro studies.
Pandey D, et al
Researchers have identified a promising natural compound candidate for targeting KRASG12D, a mutation responsible for driving some of the most aggressive cancers, including pancreatic, colorectal, and lung cancer, for which effective targeted therapies have long been lacking. Using a structure-based virtual screening approach, the team screened a library of traditional Chinese medicine compounds through molecular docking and drug-likeness profiling, then subjected the top candidates to advanced 200-nanosecond molecular dynamics simulations to assess their stability and binding potential. Among the three compounds evaluated in laboratory cell studies, Rubimaillin emerged as the standout performer, inhibiting two pancreatic cancer cell lines with IC50 values of 1.10 µM and 2.07 µM while remaining markedly less toxic to healthy human cells. Beyond simply killing cancer cells, Rubimaillin also suppressed cancer cell migration and favorably altered the expression of key cancer-related genes, reducing levels of the survival-promoting BCL2, SOX9, and LC3 while boosting expression of the tumor-suppressor p53. These results position Rubimaillin as a strong lead compound for further preclinical and clinical investigation, and illustrate the value of combining computational drug discovery tools with the rich chemical diversity of natural products in the search for new KRASG12D-targeted medicines.
Molecular diversity
Source →Leading Causes of Death Among Non-Hispanic American Indian and Alaska Native People, by Indian Health Service Area, 2020.
Melkonian SC, et al
This study examined age-adjusted death rates for 2020 among non-Hispanic American Indian and Alaska Native (AI/AN) people compared with non-Hispanic White people across all Indian Health Service (IHS) Areas, using data from the US Cancer Statistics AI/AN Mortality Database corrected for racial misclassification. Researchers found that overall death rates among AI/AN people were 90% higher than among non-Hispanic White people, with elevated rates observed in every single IHS Area studied. The disparity was most severe in the 25-to-44 age group, where AI/AN death rates were nearly four times higher than those of non-Hispanic White peers. The leading causes of death among both AI/AN males and females included COVID-19, heart disease, unintentional injury, cancer, and chronic liver disease. These findings underscore profound and persistent health inequities facing Native communities and provide critical evidence to guide public health investment, emergency preparedness planning, and targeted interventions to reduce preventable mortality.
Public health reports (Washington, D.C. : 1974)
Source →SEPHS2 loss reprograms cancer metabolism from oxidative phosphorylation to gluconeogenesis via PCK1 stabilization.
Zhang Y, et al
Researchers investigated how the selenium-metabolizing enzyme SEPHS2 controls cancer cell energy production, particularly its role in oxidative phosphorylation (OXPHOS), the oxygen-dependent process cells use to generate energy. Using a targeted genetic screen, the team found that loss of SEPHS2 suppresses OXPHOS and redirects glucose metabolism toward gluconeogenesis and the pentose phosphate pathway (PPP) rather than shutting down respiration entirely. Mechanistically, SEPHS2 loss elevates intracellular NAD+ levels, which activates the protein deacetylase SIRT2 and promotes stabilization of the gluconeogenic enzyme PCK1 through deacetylation, revealing a detailed molecular chain of events. In cancer models with reduced selenium availability—mimicking selenium-poor tumor microenvironments—SEPHS2 levels dropped and tumors showed enhanced spread to the lungs, highlighting a clinically relevant metabolic vulnerability. Crucially, tumors undergoing this metabolic reprogramming became sensitized to the PPP inhibitor 6-aminonicotinamide, pointing to a potential therapeutic strategy for cancers growing in selenium-limited conditions. These findings establish a new, selenoprotein biosynthesis-independent function of SEPHS2 and suggest that targeting the PPP may be an effective approach in patients whose tumors adapt to low-selenium environments.
Cell reports
Source →A macrophage MHC-I axis links intratumoral heterogeneity to terminal CD8+ T cell exhaustion in lung adenocarcinoma.
Yin S, et al
A new study published in NPJ Precision Oncology investigated whether intratumoral heterogeneity — the genetic diversity among cells within a single tumor — worsens immune dysfunction in lung adenocarcinoma, specifically by driving the exhaustion of cancer-fighting CD8+ T cells. Using bulk, single-cell, and spatial transcriptomics across multiple patient cohorts, the researchers found that tumors with high genetic diversity consistently exhibited more severe T cell exhaustion, and that patients bearing both traits simultaneously had the worst survival, despite their tumors carrying a higher burden of cancer-recognizable mutations. Macrophages emerged as the critical link: in genetically diverse tumors, macrophages strongly upregulated MHC-I antigen-presentation machinery and spatially clustered near the most exhausted T cells, suggesting they actively drive terminal immune dysfunction rather than productive anti-tumor immunity. A six-gene decision-tree classifier — comprising CDC45, CENPF, PCLAF, SCGB3A1, CDCA8, and NDC80 — was derived to predict a tumor's combined heterogeneity and exhaustion status, providing a potential clinical stratification tool. These findings argue for combining immune checkpoint blockade with macrophage reprogramming or modulation of antigen-processing pathways to restore effective anti-tumor immunity in patients who currently respond poorly to immunotherapy.
NPJ precision oncology
Source →PRIMA: randomized prospective multicenter non-inferiority study for primary diagnosis of clinically significant PRostate cancer by PSA and MR IMAging-study protocol for a randomized diagnostic accuracy trial.
Al-Monajjed R, et al
The PRIMA trial is a randomized, prospective, multicenter non-inferiority study being conducted at eight German hospitals to determine whether MRI-targeted biopsy alone is sufficient for detecting clinically significant prostate cancer in men who have not previously undergone biopsy. Current diagnostic pathways combining PSA testing, digital rectal examination, and systematic biopsy can both miss aggressive cancers and over-detect slow-growing, indolent disease, fueling unnecessary treatment and patient harm. In the PRIMA protocol, biopsy-naïve men aged 50–75 with elevated PSA or suspicious examination findings and abnormal multiparametric MRI results are randomly assigned to receive either targeted biopsy alone or targeted biopsy combined with systematic biopsy. The study plans to enroll 1,908 men to yield 1,590 analyzable patients, providing over 80% statistical power to test non-inferiority with a predefined margin of 13%. If targeted biopsy proves non-inferior to the combined approach, omitting systematic biopsy in MRI-positive men could reduce diagnostic morbidity, lower overdiagnosis rates, and spare thousands of patients from unnecessary procedures.
Trials
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