Latest Research
All publications from the Cancer3.AI database, newest first.
Stiffness-dependent alveolar type II cell senescence in idiopathic pulmonary fibrosis.
Lin C, et al
Researchers investigated how the mechanical stiffness of lung tissue drives cellular senescence — a state in which cells permanently stop dividing and release harmful inflammatory signals — in alveolar type II (AT2) cells, which are critical progenitor cells responsible for maintaining lung integrity. Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease characterized by excessive scarring that progressively stiffens lung tissue and severely impairs breathing, yet its underlying cellular mechanisms remain incompletely understood. The study demonstrated that increasing matrix stiffness, as occurs in fibrotic lung tissue, promotes senescence in AT2 cells in a stiffness-dependent manner, suggesting that mechanical cues from the diseased microenvironment actively drive pathological cell aging. This senescent state causes AT2 cells to release pro-fibrotic and pro-inflammatory mediators, creating a self-reinforcing feedback loop that accelerates fibrosis progression. These findings identify the mechanical stiffness-senescence axis as a key driver of IPF pathology and highlight AT2 cell senescence as a promising therapeutic target for interrupting the vicious cycle of fibrosis in patients with this incurable disease.
Cell communication and signaling : CCS
Source →METTL3-mediated m6A modification of lncRNA MALAT1 promotes colorectal cancer progression by activating the NF-κB signaling pathway.
Lin S, et al
Colorectal cancer is among the most common and deadly cancers worldwide, with poor outcomes often driven by aggressive recurrence and metastasis whose molecular underpinnings remain incompletely understood. Researchers investigated the role of METTL3, an enzyme that adds a chemical tag called N6-methyladenosine (m6A) to RNA molecules, and its relationship with a long non-coding RNA called MALAT1 in colorectal cancer progression. The study found that both METTL3 and MALAT1 are significantly overexpressed in colorectal cancer tissues, and that METTL3 stabilizes MALAT1 by installing m6A modifications on it, which in turn activates the pro-tumorigenic NF-κB signaling pathway by promoting degradation of its inhibitor IκBα and enabling nuclear entry of the p65 protein. Suppressing either METTL3 or MALAT1 in laboratory models sharply reduced cancer cell proliferation, migration, and invasion while triggering cell death, and a natural compound called trihydroxy methylcyclohexane aminoglycoside was identified as a high-affinity METTL3 inhibitor that blocked tumor growth in mice without observable toxicity. These findings establish a METTL3-m6A-MALAT1-NF-κB regulatory axis as a critical driver of colorectal cancer and provide a strong scientific rationale for developing METTL3-targeted therapies to improve outcomes for patients with this disease.
Journal of translational medicine
Source →Increasing value in the Veterans Affairs Healthcare System (VA) with precision health: a continuing landmark collaboration with the Department of Energy.
Justice AC, et al
A major federal collaboration known as MVP-CHAMPION Phase II, between the U.S. Department of Veterans Affairs and the Department of Energy, harnessed artificial intelligence, high-performance computing, and large-scale clinical, genetic, and geospatial data to advance precision health for veterans. The initiative launched eight targeted clinical projects addressing conditions including lung cancer screening, cardiovascular risk, heart failure, diabetic kidney complications, post-COVID sequelae, and medication toxicity, representing areas where AI provided a previously missing analytical capability. Researchers developed multimorbidity-aware frameworks and reusable computational pipelines that enabled identification of novel genetic risk factors and the construction of more accurate predictive models across these disease areas. These genetic discoveries are already informing drug development and repurposing efforts, while the improved prediction models hold direct promise for better clinical decision-making and earlier intervention. The infrastructure and scientific advances built across both phases of MVP-CHAMPION position this collaboration as a transformative force not only for veterans' healthcare but for the broader national adoption of AI-driven precision medicine.
Journal of the American Medical Informatics Association : JAMIA
Source →Mechanism of AGEs-RAGE axis inhibition of ferroptosis in type 2 diabetic colon cancer by regulatory CEACAM1.
Liu K, et al
This study investigated how the AGEs-RAGE signaling axis suppresses ferroptosis — an iron-dependent form of programmed cell death — in colon cancer occurring in patients with type 2 diabetes. Advanced glycation end-products (AGEs), which accumulate at abnormally high levels in diabetic individuals, activate their cell-surface receptor RAGE and appear to block ferroptotic cell death pathways in colon cancer cells, thereby helping tumors survive and proliferate. The regulatory protein CEACAM1 was identified as a key molecular mediator linking diabetic metabolic conditions to the inhibition of this cancer-suppressing death mechanism. These findings shed light on a plausible molecular explanation for the well-documented clinical association between type 2 diabetes and elevated colon cancer risk and poorer prognosis. Importantly, this research identifies the AGEs-RAGE-CEACAM1 pathway as a potential therapeutic target, suggesting that restoring ferroptosis sensitivity in diabetic colon cancer patients could improve treatment outcomes.
Scientific reports
Source →Lymphocyte Micronucleus Formation Is Driven by Inflammation-Induced Oxidative DNA Damage in Oesophageal Cancer Development.
Munn K, et al
Researchers investigated the mechanisms of DNA damage in circulating blood cells across the progressive spectrum of oesophageal disease — from gastro-oesophageal reflux disease (GORD) and Barrett's oesophagus (BO) through to oesophageal adenocarcinoma (OAC) — using a test called the lymphocyte micronucleus assay, which measures small fragments of damaged DNA inside white blood cells. Patients with OAC showed significantly higher rates of micronucleus formation compared with healthy individuals, GORD patients, and BO patients, and their lymphocytes were also more sensitive to a spindle-disrupting agent called vinblastine, pointing to both DNA strand damage and problems with chromosome segregation. The elevated micronucleus levels correlated with established blood markers of oxidative stress and inflammation — including 8-OHdG, IL-8, and 2'3'-cGAMP — as well as reduced levels of IκB protein in oesophageal tissue, collectively indicating activation of the cGAS-STING and NF-κB inflammatory signalling pathways. Interestingly, patients with already-high baseline DNA damage showed a blunted response to further oxidative challenges in the laboratory, suggesting their antioxidant defences may be exhausted or dysregulated. These findings establish a systemic, inflammation-driven mechanism of genomic instability in OAC and raise the prospect that measuring micronucleus frequency in a simple blood sample could serve as a minimally invasive biomarker for monitoring disease progression and cancer-associated genomic stress.
International journal of cancer
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