Topic: Cancer Research

Health & MedicineSeptember 22, 2026

SelO functions as a tumor suppressor through AMPylating Cdk5rap3.

Cell fate is governed by signaling pathways involving diverse protein modifications. However, how protein AMPylation mediates signal transduction in mammalian cells remains largely unexplored. We demonstrate that the protein adenylyltransferase, SELENOO (SelO), is induced by chemotherapy, and has clinical relevance in cancer. In mice, SelO knockout facilitates primary tumor development and metastasis. In cancer cells, the cytosolic fraction of SelO suppresses cell proliferation and migration. Me

Health & MedicineSeptember 15, 2026

Targeting cholesterol-dependent Piezo1 activation impairs amoeboid migration in melanoma cells.

Bleb-based migration enables cancer cells to navigate the heterogeneous tumor microenvironment. Here, we report a phenotypic screen identifying drugs that inhibit bleb formation, a driver of amoeboid migration. Statins, including Fluvastatin, suppress amoeboid migration of melanoma cells in confined environments by reducing intracellular cholesterol. This disrupts plasma membrane tension sensing by Piezo1, lowering intracellular Ca 2+ levels. Both cholesterol supplementation and Piezo1 activatio

Health & MedicineSeptember 15, 2026

Multicellular rosette formation guides epithelial tissue assembly in pancreatic ductal adenocarcinoma cell organoids.

Mesenchymal-to-epithelial transitions are essential for epithelial tissue formation and thus the development of functional organs. Here, we demonstrate that the transition from a disordered mesenchymal state to a columnar epithelial structure in branched pancreatic ductal adenocarcinoma organoids is associated with rosette formation. We show that fluctuations in acto-myosin contractions on the emerging apical side of branches with high cell density create a tug-of-war mechanism, leading to regul

Health & MedicineSeptember 14, 2026

Encoded and non-genetic protein variants expand human functional proteome.

Each stage of the Central Dogma contributes to proteome diversity through mechanisms such as heterozygosity, somatic mutations, transcriptional errors, and translational errors. As a result, a diverse array of protein variants can coexist within a single proteome, such as that of humans. However, until now, methods to detect, quantify, and evaluate the functional consequences of these variants have been lacking. Here we examined a large-scale proteogenomic dataset from 29 healthy human tissues a

Health & MedicineSeptember 14, 2026

Copper ion-induced MYH9 polymerization executes cuproptosis.

Cuproptosis is a recently identified form of copper-dependent cell death implicated in various physiological and pathological processes. However, the executive proteins involved and the role of physiological intracellular copper in cuproptosis remain unclear. Herein, we identified myosin heavy-chain 9 (MYH9) as a cuproptosis executioner. Copper binding induced MYH9 polymerization, which disrupted the actin cytoskeleton and led to cuproptotic cell death. Hexyl 2-(3,4,5-trihydroxy-phenyl) acetate

Health & MedicineSeptember 12, 2026

Tambotatug Pelitecan in Small-Cell Lung Cancer after Platinum-Based Therapy.

Tambotatug pelitecan (known as Tam-Peli, a new antibody-drug conjugate that targets the immune-checkpoint molecule B7-H3) showed promising clinical efficacy in patients with relapsed extensive-stage small-cell lung cancer in early-phase trials. In this phase 3, multicenter, open-label, randomized trial, we assigned eligible patients with small-cell lung cancer that had progressed after first-line platinum-based therapy in a 1:1 ratio to receive tambotatug pelitecan or topotecan. The primary end

Health & MedicineSeptember 11, 2026

Mitochondrial ATP promotes T cell differentiation through chromatin accessibility.

Immune elimination of chronic infection or cancer requires cytotoxic CD8 + T cells that adopt and maintain an effector phenotype. Cytotoxic T cell function is a bioenergetically demanding process. Here, we report the ability of D-α-hydroxybutyrate (DAHB) to act as a signaling molecule that increases mitochondrial ATP production and drives the conversion of proliferating T cells into cytotoxic effector cells. DAHB signaling switches ATP production from glycolysis to oxidative phosphorylatio

Health & MedicineSeptember 10, 2026

Lean adipocyte oxylipin signaling restrains breast cancer through ferroptosis.

Obesity increases breast cancer risk and tumor aggressiveness, yet the mechanisms underlying this association remain unclear. In this work, we identify a tumor-suppressive lipid signaling pathway in which mammary adipocytes secrete the oxylipin 9S-hydroxyoctadecadienoic acid (9S-HODE). 9S-HODE induces ferroptosis in breast cancer cells by disrupting iron homeostasis. Adipocytes in obese mammary tissue produce less 9S-HODE, and tumors in obese mice exhibit reduced ferroptosis. Accordingly, ferrop

Physical/TechSeptember 10, 2026

Extensive and differential platinum chemotherapy mutagenesis in livers of children.

Childhood cancer survivors often experience late adverse effects that may be linked to chemotherapy mutagenesis. We studied chemotherapy mutagenesis in normal pediatric tissues using duplex sequencing (NanoSeq) to enable the detection of mutations from single DNA molecules. We found that platinum chemotherapeutics increased the mutation burdens of normal pediatric tissues to levels seen in adults. In the liver, platinum agents imparted a tissue-specific mutational signature that was absent from

Health & MedicineSeptember 10, 2026

Chronic type II interferon promotes tumor growth through mitochondrial RNA–induced type I interferon and prostaglandin synthesis

Interferons (IFNs) are proinflammatory cytokines that promote immune cell engagement to eliminate malignant cells. Paradoxically, chronic interferon signaling can also activate anti-inflammatory mechanisms that allow cancer cells to evade the immune system. In this study, we sought to determine the cellular mechanisms underlying this switch from antitumorigenic to protumorigenic interferon activity. We show that chronic type II interferon (IFN-II) exposure distinctively induced tumor growth by a

Health & MedicineSeptember 9, 2026

An Inhalable Hybrid Nitric Oxide Nanogenerator for Lung Adenocarcinoma Treatment via Bioorthogonal-Activated Gas-Immunotherapy.

Nitric oxide (NO) holds promise for circumventing resistance to platinum-based chemotherapy by reprogramming the tumor microenvironment (TME) in lung adenocarcinoma (LUAD). However, their further application is greatly hindered by uncontrolled release kinetics and off-target toxicity. Herein, an inhalable NO nanogenerator (10m@FOMs-Cu) that reprograms the TME via specific NO release is developed by encapsulating a biorthogonal-activated NO-cisplatin prodrug into TME-responsive hybrid micelles, a

Health & MedicineSeptember 8, 2026

Intratumoral injection of EpCAM BITE, IL-12, and GM-CSF mRNA-LNPs blocks the growth of local treated and distant untreated tumors.

We have previously shown that a T cell engaging bispecific humanized anti-human EpCAM-CD3 antibody efficiently kills a human EpCAM positive human xenograft in an NSG partially humanized mouse injected intravenously with human T cells when the anti-EpCAM-CD3 was delivered intratumorally as an mRNA-LNP. To extend these results we tested the effects of combining the anti-human EpCAM-CD3 with various cytokines injected into a tumor on the left side of NSG mice and an uninjected tumor on the right si

Health & MedicineSeptember 6, 2026

Induction and consolidation atezolizumab with stereotactic body radiation therapy versus radiation alone in high-risk, early-stage non-small-cell lung cancer (SWOG/NRG S1914): a multicentre, open-labe

Stereotactic body radiation therapy (SBRT) is the standard of care for early-stage, medically inoperable non-small-cell lung cancer (NSCLC). We aimed to test the addition of neoadjuvant, concurrent, and adjuvant atezolizumab with SBRT for early-stage NSCLC. In this multicentre, open-label, phase 3, randomised controlled trial, eligible patients from 146 institutions across the USA who had T1-T3N0M0 NSCLC ≤7 cm, and were medically inoperable or declined surgery, and had at least one risk f

Health & MedicineSeptember 6, 2026

The changing therapeutic landscape of small-cell lung cancer.

Small-cell lung cancer (SCLC) is an exceptionally aggressive malignancy: highly proliferative, heterogeneous, and frequently metastatic at diagnosis. Although initially responsive to chemotherapy, such responses are typically transient, and recurrent disease has been largely refractory to standard cytotoxics. The past decade has been notable for major advances in our understanding of SCLC biology, and this preclinical progress is now informing multiple novel therapeutic approaches for this disea

EnvironmentSeptember 3, 2026

Psilocybin prevents chemotherapy-induced peripheral neuropathy through mitochondrial trafficking preservation.

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling, often irreversible toxicity that affects millions of patients, limits life-saving cancer therapy, and lacks proven treatment. In this work, we show that as little as two doses of psilocybin before chemotherapy durably prevented the onset of CIPN across platinum- and taxane-based models, including repeated chemotherapy cycles, without impairing antitumor efficacy. Peripherally, psilocybin maintained tactile sensitivity and intraepi

Health & MedicineSeptember 3, 2026

Tumor-derived antioxidants suppress immunity by depriving T cells of reactive oxygen species

Reactive oxygen species (ROS) promote genomic instability and fuel oncogenic signaling in cancer, but antioxidant therapies have so far failed to improve, or worsen, cancer outcomes. Emerging data suggest that T cells depend on ROS for signal transduction. In this study, we show that tumors exploit this dependency, releasing antioxidant enzymes into the tumor environment to suppress T cell–mediated antitumor immunity. The interstitial fluid of tumors possesses potent antioxidant activity, associ

Health & MedicineSeptember 1, 2026

Atezolizumab in early triple-negative breast cancer: the randomized phase 3 NSABP B-59/GeparDouze trial.

Triple-negative breast cancer (TNBC) is an aggressive subtype with an activated tumor immune microenvironment. The multicenter, multinational, double-blinded NSABP B-59/GeparDouze trial evaluated the addition of atezolizumab (atezo) (773 patients randomized) or placebo (777 patients) to sequential taxane-carboplatin-anthracycline-based neoadjuvant chemotherapy in stage II-III TNBC. The addition of atezo did not significantly improve the primary endpoint of event-free survival (EFS) (HR, 0.80 (95

Health & MedicineAugust 27, 2026

Generalised eruptive histiocytosis mimicking lymphoma relapse in a patient with previous diffuse large B-cell lymphoma.

A 92-year-old man with a history of diffuse large B-cell lymphoma treated with chemoradiotherapy, and later with radiotherapy for an isolated cutaneous relapse with complete response, presented with a 1-month history of multiple asymptomatic erythematous-to-violaceous papules and nodules on the face, trunk, and upper limbs. Given his oncological history and previous skin involvement, lymphoma relapse was the leading diagnostic concern, with cutaneous metastases and sarcoidosis also considered. H

Health & MedicineAugust 25, 2026

Neonatal diethylstilbestrol exposure disrupts uterine epithelial apical-basal polarity and partial EMT state.

The developing female reproductive tract is highly sensitive to external hormonal stimulation, which can result in infertility and gynecologic diseases. To determine the underlying mechanisms, we used a mouse model to test the direct, cell type-specific effects of neonatal exposure to the estrogenic chemical, diethylstilbestrol (DES), on the developing uterus. We found that control uterine epithelium is in a partial epithelial-mesenchymal transition state that is lost following DES exposure. Thi

Health & MedicineAugust 25, 2026

Proliferation as a natural strategy to suppress neoplasia.

Cell proliferation is necessary to maintain tissue homeostasis, but proliferation carries with it a risk of cancer. To understand how some organisms suppress cancer while maintaining homeostasis, we developed a dynamical model of cell populations. The model identifies two regimes. In one regime, as expected, proliferation drives accumulation of neoplastic cells. In another regime, unexpectedly, increasing proliferation suppresses accumulation of neoplastic cells. In this regime, as more cells pr

Health & MedicineAugust 25, 2026

Loss of Sox10 prevents tumor initiation in vivo and induces luminal-to-basal reprogramming in Neu+ tumor cells.

The SRY-HMG-Box transcription factor SOX10 plays a critical role in neural crest development, but its function in epithelial tumorigenesis remains unclear. Here, we identify SOX10 as a key regulator of tumor-initiating activity in Neu-driven mammary cancers. Genetic ablation of Sox10 in the luminal compartment of MMTV-Neu (NIC) mice resulted in delayed but normal mammary gland development. Sox10 deletion resulted in a reduction in mammary progenitors and a complete loss of tumor initiation in So

Health & MedicineAugust 22, 2026

Liver resection after atezolizumab and bevacizumab versus maintenance therapy for locally advanced hepatocellular carcinoma (TALENTOP): a multicentre, open-label, randomised, phase 3 trial.

Resection might offer additional benefit in patients with advanced-stage hepatocellular carcinoma treated with systemic therapy. However, high-quality evidence supporting the procedure is absent. We aimed to establish whether resection can provide survival benefit in patients with advanced hepatocellular carcinoma who respond to systemic therapy. In this randomised, open-label, multicentre, phase 3 trial, we recruited treatment-naive patients with hepatocellular carcinoma, macrovascular invasion

Physical/TechAugust 20, 2026

A cinnamyl alcohol dehydrogenase–like scaffold organizes monoterpenoid indole alkaloid biosynthesis

Biosynthesis of ~3000 monoterpenoid indole alkaloids (MIAs), including the anticancer drug vinblastine, involves the highly unstable intermediate strictosidine aglycone. Its formation by strictosidine β-glucosidase (SGD) and subsequent conversion by geissoschizine synthase (GS) occur in spatially separated compartments, representing a major biosynthesis bottleneck. In this study, we discover VinBLAST, a cinnamyl alcohol dehydrogenase–like protein repurposed as a scaffold for efficient processing

Health & MedicineAugust 18, 2026

A phosphorylation switch governs KIF11's mechanical output during mitosis.

The kinesin-5 motor protein KIF11 is crucial for mitotic spindle assembly, driving the separation of spindle poles through microtubule sliding. Src-family kinases phosphorylate KIF11 at multiple tyrosine residues within its motor domain, but the mechanistic consequences of these modifications remain unclear. Here, we dissect the role of phosphorylation at Y211 using phospho-mimetic (Y211E) and nonphosphorylatable mutants (Y211F) in biochemical, biophysical, and cellular assays. Optical trapping

Health & MedicineAugust 18, 2026

Cryptic small-molecule binding sites in the ARID1B DNA-binding domain.

Genetic depletion of ARID1B has been shown to act in a synthetically lethal manner to selectively kill cancer cells with mutations in the tumor suppressor ARID1A, one of the most frequently altered proteins in human cancer. However, no precision therapeutic targeting ARID1B in ARID1A-mutant cancer has been developed due to the lack of a classically druggable small-molecule binding pocket on ARID1B. Here, we carried out molecular dynamics simulations on the small, globular AT-rich Interaction Dom

Health & MedicineAugust 18, 2026

Inflammatory kinase TBK1 suppresses homologous recombination DNA repair to sensitize tumors to chemotherapy.

Inflammation exerts context-dependent influences on tumor progression and therapeutic response. Although chemotherapy remains a cornerstone of cancer treatment, its functional interplay with inflammatory signaling is still incompletely understood. Here, we identify TANK-binding kinase 1 (TBK1) as a critical modulator of chemotherapeutic efficacy through its impact on DNA damage repair. TBK1 activation potentiates cancer-cell death induced by chemotherapeutic agents by promoting DNA damage and im

Health & MedicineAugust 15, 2026

Efficacy and safety of upadacitinib in adults and adolescents for treatment of non-segmental vitiligo (Viti-Up): results of two phase 3 randomised controlled studies.

Non-segmental vitiligo is an autoimmune inflammatory disease characterised by loss of melanocytes leading to skin depigmentation. No systemic therapies have been approved, and additional therapeutic options are needed. Here, we report the efficacy and safety of upadacitinib, a selective once-daily Janus kinase inhibitor, in adults and adolescents with non-segmental vitiligo. Viti-Up includes two phase 3, global, multicentre, randomised, double-blind, placebo-controlled studies conducted at 138 i

Health & MedicineAugust 12, 2026

Biomarkers of nivolumab benefit in resectable non-small cell lung cancer.

Perioperative nivolumab significantly improved event-free survival (EFS) compared with placebo in patients with resectable non-small cell lung cancer (NSCLC) in the CheckMate 77T study (ClinicalTrials.gov NCT04025879 ) 1 . Here, after randomization, 98 out of 229 patients who received nivolumab and 92 out of 232 patients who received placebo had evaluable biomarkers (41% of randomized patients). Of the 98 patients receiving nivolumab, 83 (85%) had detectable circulating tumour DNA (ctDNA) before

Health & MedicineAugust 12, 2026

First-line PD-1/VEGF bispecific antibody plus chemotherapy in triple-negative breast cancer: a phase 2 trial.

Triple-negative breast cancer is an aggressive subtype comprising 10-20% of all breast cancer cases and has a worse prognosis than other subtypes. This open-label, multicenter, single-arm, phase 2 clinical trial evaluates the safety and efficacy of ivonescimab combined with chemotherapy as first-line treatment in female patients with locally advanced unresectable or metastatic triple-negative breast cancer who have not received previous systemic therapy. Eligible patients received ivonescimab 20

Health & MedicineAugust 10, 2026

Liquid Biopsies for Cancer: A Translational Science Review.

Circulating tumor DNA (ctDNA) evaluation, in which fragments of tumor DNA circulating in a patient's bloodstream are extracted and analyzed, can be used to monitor cancer progression, detect residual cancer after treatment, and identify genetic changes within cancer cells that could affect treatment response. ctDNA sequencing identifies cancer cell gene variants that inform the selection of molecularly directed therapies in several types of cancer, including non-small cell lung cancer, colorecta