Drug Database
FL

fluorouracil (Carac, microsponge)

✓ Approved

Heron Therapeutics, Inc. · TYMS · Small Molecule

What is fluorouracil?

fluorouracil is a small molecule developed by Heron Therapeutics, Inc.. It is approved for therapeutic indications via transdermal.

Drug Profile

Brand NamesCarac, microsponge
CompanyHeron Therapeutics, Inc.
Drug ClassSmall Molecule
Molecular TargetTYMS
RouteTransdermal
StatusApproved

Mechanism of Action

Molecular Targets

fluorouracil acts on 1 molecular target:

TYMSthymidylate synthetase (DKCD, TMS)
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Therapeutic Indications

fluorouracil is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Skin and subcutaneous tissue disordersActinic keratosis✓ Approved

Related Research Articles

PubMediScience2026-08-30

BOLD-100 treatment induces systemic lipid crosstalk in metastatic colorectal carcinoma patients in a combination treatment with FOLFOX.

Borutzki Yasmin Y, Hagn Gerhard G, Bileck Andrea A, Mohr Thomas T et al.

BOLD-100 (sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)]) is a clinical-stage anticancer drug candidate that targets glucose-regulated protein (GRP78) and impacts the endoplasmic reticulum (ER) stress responses in cancer cells. Despite expanding knowledge about its multimodal mechanism of action from preclinical studies, little is known about the metabolic effects of BOLD-100 in patients. This study is an exploratory analysis of the blood plasma from a subset of metastatic colorectal carcinoma (mCRC) patients who were participants in a phase 1b/2a dose-escalation study (NCT04421820) using a multi-omics strategy based on proteomic and lipid analyses. BOLD-100 treatment was found to exhibit systemic, dose-dependent effects that were more pronounced on the lipid level compared with the protein level. This study indicates that BOLD-100 affects lipid profiles and influences systemic lipid crosstalk, which, in combination with oxaliplatin, leucovorin, and fluorouracil (FOLFOX) chemotherapy may, at least partially, account for the superior clinical outcomes over established therapies in mCRC patients.

PubMedBiochimica et biophysica acta. Reviews on cancer2026-08-30

Systemic therapy-induced resistance and toxicity in breast cancer: Sensitization and mitigation strategies.

Samudrala Anuveda Sree AS, Nagaraju Ganji Purnachandra GP, Malla RamaRao R

Breast cancer is the most frequently reported cancer in women, with high mortality and morbidity globally. Paclitaxel, doxorubicin, tamoxifen, cisplatin, and 5-fluorouracil are cornerstones of standard-of-care treatment for primary and advanced breast cancers, targeting distinct molecular mechanisms. However, the evolution of acquired resistance primarily leads to treatment failure and progression to metastasis, ultimately to patient mortality. Furthermore, their effectiveness is limited by potential toxicities in various organs. These limitations present an extreme challenge for the management of breast cancer at the advanced stage. This review uncovers recent updates on acquired resistance mechanisms toward standard-of-care treatments driven by deeply rooted heterogeneity and aggressive nature through direct counteracting of its core action, hyperactivation of survival pathways, silencing of core cell death pathways, derepressing the expression of multidrug resistance proteins, metabolic reprogramming, epigenetic modifications, and exosome-mediated horizontal transfer of resistance phenotype. In addition, we discuss recent updates on potential strategies to overcome resistance and toxicities induced by standard-of-care treatments. Ultimately, this review helps to identify novel strategies targeting pathways to reverse resistance and reduce toxicity in breast cancer patients.

PubMedMarine life science & technology2026-08-30

A marine-derived meroterpenoid inhibits colorectal cancer via PI3K pathway modulation in mice.

Han Ming-Qian MQ, Zhang Ji-Chao JC, Zhao Ying-Jie YJ, Liu Yun-Feng YF et al.

Colorectal cancer is among the most leading cancers in China, characterized by activating mutations in PIK3CA or aberrant AKT signaling in approximately 30%-40% of cases. Marine natural products, especially those derived from marine fungi, offer a valuable source of novel phosphatidylinositol 3-kinase (PI3K) inhibitors. In this study, two novel phenylspirodrimane-type meroterpenoids, chloropenoids A and B (1 and 2), along with ten known analogues (3-12), were isolated from the marine-derived fungus Stachybotrys chlorohalonatus. The absolute configurations of 1 and 2 were established by time-dependent density functional theory electronic circular dichroism (TDDFT-ECD) calculations. Structural optimization via esterification at the C-2' position of 3 generated a series of derivatives (3a-3i), among which derivative 3a displayed potent antiproliferative activity against CT-26 colorectal cancer cells. Mechanistic studies revealed that 3a disrupted mitochondrial membrane potential, induced apoptosis (total apoptosis rate: approximately 32% at 12.50 μM), and induced G1-phase cell cycle arrest. Molecular docking and Western blot assays demonstrated that 3a effectively inhibited PI3K phosphorylation, consequently attenuating the PI3K/AKT/mTOR signaling cascade. In vivo evaluation using a BALB/c mouse xenograft model revealed that intraperitoneal administration of 3a (50 mg/kg/day for 10 days) significantly suppressed tumor growth (Tumor Growth Inhibition = 85.2%) compared with the control group, exhibiting superior efficacy and reduced systemic toxicity compared to the standard chemotherapy drug, 5-fluorouracil. These findings identify compound 3a as a promising candidate for further development as a PI3K inhibitor for colorectal cancer therapy and provide critical mechanistic insights into phenylspirodrimane-based antitumor agents. The online version contains supplementary material available at https://doi.org/10.1007/s42995-026-00356-7.

PubMedActa biomaterialia2026-08-30

An Immune-Activated Co-culture Model of Patient-Derived Gastric Cancer Organoids and Peripheral Blood Mononuclear Cells for Personalized Chemotherapy Screening.

Yu Yefan Y, Chen Wei W, Jia Ningfei N, Wang Chen C et al.

Selecting effective chemotherapy after immunotherapy remains a major clinical challenge in advanced gastric cancer because patient responses are highly heterogeneous. A major obstacle is the lack of personalized preclinical models that faithfully recapitulate the immune-activated tumor microenvironment (TME) following immunotherapy and enable evaluation of subsequent chemotherapy responses while preserving immune-tumor interactions. Here, we developed an immune-activated co-culture model comprising patient-derived gastric cancer organoids and autologous peripheral blood mononuclear cells (PBMCs). Immune activation was achieved using anti-PD-1-loaded gold nanocages (aPD-1@Au NCs), which integrate near-infrared-triggered photothermal tumor ablation with sustained anti-PD-1-mediated immune modulation. The resulting model recapitulates key features of the post-immunotherapy TME, including enhanced immune-cell infiltration, increased tumor-cell apoptosis, and CD8+ T-cell activation. We then applied this model to evaluate five clinically relevant chemotherapeutic agents, including oxaliplatin, irinotecan, fluorouracil, doxorubicin, and docetaxel, for personalized chemotherapy screening after immunotherapy. Compared with monoculture organoids or non-activated co-cultures, the immune-activated model revealed drug-specific differences in tumor-killing efficacy, immune-mediated chemosensitization, and PBMC toxicity. Among the tested agents, oxaliplatin showed the strongest immune-mediated chemosensitization, whereas docetaxel achieved favorable tumor cell killing with relatively low immunotoxicity. These findings demonstrate that chemotherapy responses after immune activation are highly drug-specific, underscoring the importance of personalized chemotherapy selection following immunotherapy. As a proof-of-concept study, this work establishes an immune-activated patient-derived gastric cancer organoid-PBMC co-culture model that partially recapitulates the post-immunotherapy TME. This model provides a promising framework for developing personalized chemotherapy screening strategies after immunotherapy. STATEMENT OF SIGNIFICANCE: Selecting effective chemotherapy after immunotherapy remains a major challenge in advanced gastric cancer because of substantial interpatient heterogeneity. Progress in personalized treatment is limited by the lack of preclinical models that faithfully recapitulate the post-immunotherapy tumor microenvironment (TME). Here, we developed an immune-activated co-culture model integrating patient-derived gastric cancer organoids with autologous peripheral blood mononuclear cells (PBMCs). Immune activation was achieved using anti-PD-1-loaded gold nanocages (aPD-1@Au NCs), which combine near-infrared-triggered photothermal tumor ablation with sustained aPD-1-mediated immune modulation. This platform preserves patient-specific tumor characteristics while capturing key immune-tumor interactions following immunotherapy. Using this model, we evaluated five clinically relevant chemotherapeutic agents and identified distinct drug-specific differences in tumor-killing efficacy, immune-mediated chemosensitization, and immunotoxicity. As a proof-of-concept study, this work establishes a promising framework for personalized chemotherapy screening after immunotherapy and supports the development of precision treatment strategies for gastric cancer.

PubMedAnnals of surgical oncology2026-08-30

Post-pancreatectomy Liver Injury After Mayo Clinic Class Ia Celiac Axis Resection: Illustration of This Newly Described Entity with Delayed Hepatic Artery Revascularization.

Garnier Jonathan J, Amabile Philippe P, Palen Anaïs A, Gonzalez Frederic F et al.

Resection of the celiac artery (CA) during surgery for locally advanced pancreatic cancer (LAPC) carries a significant risk of hepatic and gastric ischemia.1,2 In addition, in the current context, where patients undergo intensive chemotherapy before surgery, a new complication has emerged: post-pancreatectomy liver injury (PPLI).3 PATIENT AND METHODS: A 59-year-old patient with biopsy-confirmed locally advanced pancreatic cancer arising from the pancreatic body (Video and Fig. 1) underwent extended neoadjuvant FOLFIRINOX (folinic acid [leucovorin], fluorouracil, irinotecan, and oxaliplatin). The patient was restaged using the A-B-C criteria,4 adding the target approach for anatomical feasibility,5 metabolic imaging, and survival prediction.6 Fig. 1 Preoperative planning and first operation: extended pancreatosplenectomy, including resection of the left adrenal gland and the celiac artery (CA) (Mayo Clinic class Ia), divestment of the superior mesenteric artery, and portal vein (PV)-superior mesenteric vein reconstruction using a left renal vein graft interposition (A and B). Abdominal phase computed tomography scan, axial view, showing the encasement of the CA but with a free proper hepatic artery (PHA) as a "suitable target" if needed. (C) Drawing of the tumoral involvement with CA encasement and left/anterior side of the superior mesenteric artery (SMA) abutment. PHA, gastroduodenal artery (GDA), and the biliary tract were free of tumor, allowing a Mayo Clinic class Ia CA resection. 15 mm was the distance measured from the tumor to the GDA, and 28 mm was the distance of SMA abutment on the left side. (D) Operative view highlighting the common hepatic artery (CHA) stump, the remnant head of the pancreas (HoP), the venous reconstruction with left renal vein interposition graft, SMA divestment, and the CA stump. IVC, inferior vena cava; LGA, left gastric artery; LGV, left gastric vein; LRV, left renal vein; SA, splenic artery; SMV, superior mesenteric vein PERIOPERATIVE MANAGEMENT: The patient underwent extended pancreatosplenectomy, including resection of the left adrenal gland and the CA (Mayo Clinic class Ia), divestment of the superior mesenteric artery, and portal-superior mesenteric vein reconstruction using a left renal vein graft interposition. Arterial reconstruction was initially deemed unnecessary, as proper hepatic artery flow was maintained-albeit dampened-via the gastroduodenal artery, confirmed by visual inspection and Doppler ultrasound. Postoperatively, the course was notable for a rapid rise in alanine aminotransferase levels without overt clinical or radiological deterioration (Fig. 2). Emergency re-exploration was undertaken with the objective of hepatic arterial revascularization (Fig. 3). We hypothesized that, in the setting of underlying metabolic dysfunction-associated steatotic liver disease, arterial inflow was insufficient to meet the demands of an already vulnerable parenchyma, with increased intrahepatic resistance further compounding ischemic liver injury consistent with clinically relevant (CR)-PPLI. Liver biopsy confirmed acute steatohepatitis and extensive ischemic necrosis. Fig. 2 Postoperative liver enzyme kinetics during the first postoperative week. Alanine aminotransferase (ALT) levels demonstrated a sharp and rapid increase from the day of surgery to postoperative day (POD) 2, leading to re-operation for a supercharged hepatic artery (HA) revascularization. Following revascularization, ALT levels decreased promptly, with complete normalization of liver biochemical parameters by POD 7. AST, aspartate aminotransferase; CAR, celiac artery resection; INR, international normalized ratio POD, postoperative day Fig. 3 Second surgical procedure: final reconstruction and liver biopsy. (A) Drawing of the final reconstruction with a zoom (B) on the arterial bypass between the right renal artery and the common hepatic artery. (C) Liver biopsy showing acute steatohepatitis, with 75% macro- and micro-vesicular steatosis and extensive ischemic necrosis. (D) Zoom on the area of ischemic necrosis, showing infiltration of the liver by neutrophils, lymphocytes, and plasma cells. CA, celiac artery; CHA, common hepatic artery; GDA, gastroduodenal artery; GSV, great saphenous vein; HoP, head of pancreas; IVC, inferior vena cava; LGA, left gastric artery; LGV, left gastric vein; LRV, left renal vein; PHA, proper hepatic artery; PV, portal vein; RRA, right renal artery; RRV, right renal vein; SMA, superior mesenteric artery; SMV, superior mesenteric vein CONCLUSION: Early postoperative recognition and grading of CR-PPLI is critical to prevent liver failure, as static imaging may fail to reflect dynamic hepatic perfusion. A disproportionate rise in alanine aminotransferase within 48 h is a key warning sign. Prospective multicenter studies are needed to better define the incidence, risk factors, and optimal management of CR-PPLI.

PubMedGenetics research2026-08-29

Integrated Bulk and Single-Cell Transcriptomic Analyses Identify a Five-Gene Signature Associated With Prognosis and the Tumor Microenvironment in Epstein-Barr Virus-Associated Gastric Cancer.

Jin Lufei L, Jiang Man M, Pan Yubin Y, Wang Yan Y et al.

Epstein-Barr virus-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer, but reliable biomarkers linking EBV-related biology, prognosis, and microenvironmental remodeling remain limited. Differentially expressed genes associated with EBVaGC were identified from TCGA and GEO datasets. Weighted gene co-expression network analysis and machine learning were used to screen core genes. Functional enrichment, diagnostic and prognostic modeling, immune infiltration analysis, single-cell transcriptomic analysis of a public scRNA-seq dataset, cell-cell communication analysis, drug sensitivity prediction, external cohort validation, and RT-qPCR validation in gastric cancer cell lines were subsequently performed. Five core genes (ASPA, CHODL, GNG7, P2RY14, and PI16) were identified. The combined classifier showed high apparent diagnostic performance in the discovery datasets (AUC = 1.000 in the EBV cohort and 0.981 in TCGA-STAD) and retained value in GSE27342 (AUC = 0.771). RT-qPCR confirmed differential expression of these genes between a gastric epithelial cell line and a gastric cancer cell line, providing general tumor-versus-normal experimental support rather than EBV-specific validation. A five-gene risk signature stratified overall survival, with 1-, 2-, and 3-year AUCs of 0.634, 0.645, and 0.622, which improved to 0.716, 0.768, and 0.693 after integration with age and stage. Single-cell analysis localized the strongest signature signal to fibroblasts and B cells and revealed enhanced MIF-, PTN-, and TNFSF13B-related communication in tumors. High-risk tumors showed higher predicted IC50 values for paclitaxel and 5-fluorouracil. We identified a five-gene signature with strong diagnostic value and biologically meaningful prognostic relevance in EBVaGC, highlighting fibroblast- and B-cell-associated microenvironmental programs in aggressive disease.

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