5-fluorouracil / Generic mfg. - LARVOL DELTA

M24-311: Study to Assess Adverse Events and Change in Disease Activity in Previously Treated Adult Participants Receiving Intravenous (IV) ABBV-400 With Unresectable Metastatic Colorectal Cancer in Combination With IV Fluorouracil, Folinic Acid, and Bevacizumab (clinicaltrials.gov) - P2 | N=280 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment closed • Colorectal Cancer • Oncology • Solid Tumor

Identifying actionable genetic mutations and microsatellite instability in liquid biopsy of colorectal cancer. (PubMed, J Genet Eng Biotechnol) - "CRC genetic mutational statuses as well as contributing environmental stress factors such as gut microbiota dysbiosis are prognostically crucial, associated with high risk potential of gene-environment interactions based on machine learning."

Journal • Liquid biopsy • Colorectal Cancer • Infectious Disease • Microsatellite Instability • Oncology • Solid Tumor • FGFR3 • KDR • MSI • PIK3CA • TP53

A predictive model for life-threatening fluoropyrimidine toxicity based on DPYD sequencing in colorectal cancer. (PubMed, J Natl Cancer Inst) - "DPYD sequencing identified additional relevant variants and improved the sensitivity of DPYD testing. An online calculator (https://fluoropyrimidine-toxicity-predictor.gustaveroussy.fr/) is provided to estimate the individual probability of developing life-threatening toxicity, based on clinical covariates and extended DPYD genotype."

Journal • Colorectal Cancer • Hematological Disorders • Oncology • Solid Tumor • DPYD

RASolute 302: Phase 3 Study of Daraxonrasib (RMC-6236) in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) (clinicaltrials.gov) - P3 | N=501 | Active, not recruiting | Sponsor: Revolution Medicines, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Characterization of pityriasis rubra pilaris with hematological malignancies: Paraneoplastic disease and targeted therapy reactions (ASH 2025) - "The ALL patient was related to ponatinib, the non-Hodgkin's lymphoma case was related to copanlisib, 2 CLL patients were related to duvelisib, and 2 CLL were related to idealisib...With regards to paraneoplastic treatment, topical treatment included corticosteroids, emollients, topical urea, retinoids, and fluorouracil. Systemic treatments included methotrexate, systemic corticosteroids, and phototherapy...Specialists should maintain a high index of suspicion for PRP as a paraneoplastic signal or drug-related adverse event. Future studies are needed to elucidate such presentations and guide management."

Chronic Lymphocytic Leukemia • Dermatology • Dermatopathology • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology

Dual Cardiotoxicity of Capecitabine: Coronary Vasospasm and QT Prolongation in a Patient with Gastric Adenocarcinoma. (PubMed, JACC Case Rep) - "This case illustrates the dual cardiotoxicity of capecitabine, with both vasospastic angina and QT prolongation."

Journal • Cardiovascular • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pain • Pulmonary Disease • Solid Tumor

Impact of Neoadjuvant Chemotherapy on Perioperative Tumor Marker Dynamics and Postoperative Recovery in Patients Undergoing Laparoscopic Radical Resection for Rectal Cancer. (PubMed, J Gastrointest Cancer) - "Neoadjuvant chemotherapy prior to laparoscopic radical resection for rectal cancer was associated with improved anus preservation, enhanced postoperative recovery, and greater biochemical and functional benefits without increasing major complication rates, although it was linked to higher hematologic adverse events and postoperative declines in immune cell counts."

Biomarker • Journal • Retrospective data • Colorectal Cancer • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Rectal Cancer • Solid Tumor • CA 19-9 • CD4 • CD8

Surgery for Locally Advanced Pancreatic Cancer: Oncological Landmarks for Venous and Arterial Reconstruction. (PubMed, Ann Surg Oncol) - "We implement an extended neoadjuvant regimen-typically a minimum of eight cycles of FOLFIRINOX-aiming for normalization of CA19-9 levels...IMV, inferior mesenteric vein; LGV, left gastric vein; SMA, superior mesenteric artery artery; SV, splenic vein; SMV, superior mesenteric vein; RHA, right hepatic artery Prioritizing tumor biology, meticulous preoperative planning, and attention to key vascular technical details to ensure radical resection represent our three core oncologic landmarks. Further international, multicenter studies are needed to validate and promote the standardization of surgery for BR-PC and LAPC."

Journal • Hepatocellular Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CA 19-9

Malignancy-associated internal jugular venous thrombosis following chemoradiation for oropharyngeal carcinoma (ASH 2025) - "Six months prior, he was diagnosed with HPV-positive (p16+) oropharyngeal SCC with nodal involvement, treated with carboplatin/fluorouracil chemotherapy and 14 days of radiation...Anticoagulation choice (apixaban) required careful consideration of renal function and bleeding risk (history of GI toxicity, anemia). This case underscores the heightened thrombotic risk in HNSCC patients due to the confluence of disease biology, aggressive local therapy, and patient-specific factors like CKD. Vigilance for atypical UEDVT presentations and individualized anticoagulation strategies are crucial in this complex population."

Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Head and Neck Cancer • Hypertension • Immunology • Infectious Disease • Metabolic Disorders • Nephrology • Oncology • Oropharyngeal Cancer • Renal Disease • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thrombosis • Venous Ulcer

Trilaciclib for the prevention of chemotherapy-induced myelosuppression: A systematic review and meta-analysis (ASH 2025) - "Chemotherapy regimens were heterogeneous and included etoposide-platinum (E/P) (either cisplatin or carboplatin) (n=5), gemcitabine/carboplatin (GCb) (n=2), topotecan (n=2), FOLFOXIRI (n=1), and Carboplatin/Paclitaxel/Tislelizumab (n=1)...It also showed a positive impact on progression-free and overall survival, without compromising chemotherapy effectiveness or increasing toxicity. These findings highlight Trilaciclib's potential as a valuable adjunct to chemotherapy in appropriately selected patients."

Retrospective data • Review • Breast Cancer • Colorectal Cancer • Febrile Neutropenia • Infectious Disease • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia • Triple Negative Breast Cancer

Transfusion independence, hematological improvement and associated safety outcomes with bexmarilimab and azacitidine in HR-MDS: Results of the bexmab Phase 1/2 study (ASH 2025) - "In addition, pre-clinical datafrom Clever-1 knock-out and anti-Clever-1 treated mice suggests improved hematopoiesis andhematological recovery after 5-fluorouracil based chemotherapy. Altogetherthese data suggest that Clever-1 inhibition with the bexmarilimab combination enables hematopoieticrecovery in MDS patients. ConclusionMaintenance of baseline TI status, increased TI rate and increased number of BM progenitor cellsproducing platelets and RBCs, support bexmarilimab's unique mechanism of action in HR MDS,improving the efficacy of HMAs and supporting hematopoietic recovery, associated with lower rate ofadverse events."

Clinical • P1/2 data • Leukopenia • Myelodysplastic Syndrome • Neutropenia • AVEN

A flk-independent pathway of megakaryopoiesis is differentially responsive to stress and can produce high proportions of functionally distinct platelets (ASH 2025) - "We also challenged mice with partial myeloablation using 150 mg/kg5-fluorouracil (5-FU) or sublethal 4Gy total body irradiation (TBI) to determine the role of the Flk-indeppathway in rebuilding the hematopoietic system...This analysis revealed increased sensitivity ofFlk-indep platelets to stimulation by TLR7 (Loxoribine) and thromboxane/P2Y12 receptor agonists(U46619/ADP) in healthy young mice and after TBI treatment. Together, these data indicate that the Flk-independent pathway of hematopoietic differentiation is more complex than previously recognized,operational in healthy young adult mice, and rapidly upregulated by different hematopoietic stresses tomodulate the proportions of circulating Flk-indep platelets, as well as the contribution to other lineages,which may have both short-term and long-term functional consequences."

Thrombosis • CCR7 • CD48 • FLT3 • FOXM1 • TLR7

Lipid deregulation impacts hematopoietic stem cell functions during aging (ASH 2025) - "To understand the effect of reduced Taz expression on HSC functions, we useda doxycycline inducible, sh-RNA mediated TAZ knock-down (KD) mouse model...In competitive transplant assay, while mid-agedWT HSC treated with vehicle gave rise to a myeloid-bias graft, Alcar supplemented mid-aged WT HSC gaverise to a more balanced graft with increased ratio of lymphoid to myeloid cells in the peripheral blood 16weeks following transplantation, albeit the rescue was partial.This study indicates that HSC lipid composition becomes abnormal with aging which causes a decline inHSC function and highlights the critical role of mitochondrial CL in HSC functions. It implies thatmetabolite supplementation is a viable option for restoring age-related HSC functional defects."

Bone Marrow Transplantation • Hematological Disorders • TAFAZZIN

Jagged-1+ damage-resistant myeloid progenitors initiate the recovery of the bone marrow endothelial-niche (ASH 2025) - "We've also employed a cell-free method to re-establish vascular recovery utilizing non-fusogenic nanoparticles coated with Jag1 toenhance hematopoietic and endothelial viability following irradiation. Thus, DR-MDPs are a novel myeloidpopulation that relies on active Jag1 and Ccr2/Ccl2 signaling to provide robust recovery to the BMendothelium following myeloablative treatments."

Bone Marrow Transplantation • Hematological Malignancies • CCL2 • CCR2 • JAG1

Netrin-1 regulates hematopoietic stem cell function via UNC5A (ASH 2025) - "Furthermore, UNC5AgKO mice were unable to recover following sublethalchemotherapy (150 mg/kg of 5-fluorouracil)...Following competitivetransplantation, control mice which received NTN1 displayed a 3-fold increase in engraftment comparedto their vehicle control counterparts, whereas UNC5AgKO mice were unresponsive to NTN1. These datademonstrate that NTN1 improves HSC functionality but is unable to do so when UNC5A is knocked out,indicating that NTN1 administration results in hematopoietic rejuvenation by intrinsic HSC signaling viaUNC5A."

NTN1 • PTPRC

Finding ferritin footprints in 5-fluorouracil-induced cardiotoxicity (ASH 2025) - "MethodsWe performed a retrospective chart review on patients aged 18 and older receiving 5-FU-basedintravenous chemotherapy (including 5-FU, FOLFOXIRI, FOLFIRI, FOLFIRINOX) at a single academic centerfrom June 1, 2022 to June 1, 2024...Should ferritin be elevated, we advise clinicians to maintaina high index of suspicion for obstructive CAD and heart failure. Larger multi-institutional studies onbiomarkers predicting cancer therapy-related cardiovascular toxicity or treatment failure rates meritfuture consideration."

Congestive Heart Failure • Coronary Artery Disease • Gastrointestinal Cancer • Heart Failure

CDK4/6 inhibition mitigates chemotherapy-induced expansion of TP53-mutant clonal hematopoiesis (ASH 2025) - "We hypothesized that by protecting HSPCs from the cytotoxic effects of chemotherapy,trilaciclib might also reduce the clonal expansion of TP53-mutant CH during chemotherapy.We obtained serial blood samples from healthy controls (n=176) and three placebo-controlledrandomized clinical trials of trilaciclib including patients with (1) SCLC (n=65) receiving carboplatin andetoposide, (2) metastatic colorectal cancer (mCRC) (n=125) receivingleucovorin/fluorouracil/oxaliplatin/irinotecan (FOLFOXIRI) plus bevacizumab, and (3) metastatic triplenegative breast cancer (mTNBC) (n=34) receiving gemcitabine and carboplatin...Similar effectswere seen with the oral CDK4/6 inhibitor palbociclib and using a dominant negative form of CDK6introduced into p53 mutant HSPCs.Single cell RNA-seq of chimeric mice treated with carboplatin with trilaciclib or single agent controlsrevealed that CDK4/6 inhibition treatment promotes HSC and myeloid progenitor quiescence whilemitigating the myeloid..."

Breast Cancer • Colorectal Cancer • Eye Cancer • Hematological Malignancies • Lung Cancer • Retinal Disorders • Retinoblastoma • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • PTPRC • TP53

Macrophages mediate hematopoietic stem cell trans-endocytosis to coordinate regenerative stress and aging (ASH 2025) - "However, when CD169-/- mice were challenged with 5-fluorouracil to inducemyeloablation, we observed significantly altered HSC response with dysregulated self-renewal anddifferentiation during regeneration...Strikingly, aged CD169-/- mice exhibited dramaticexpansion of HSCs (~87.5-fold change), and significant increases of long-term reconstitution followingcompetitive BM and sorted HSC transplantations. Collectively, our data have uncovered a role for BMmacrophages in mediating HSC trans-endocytosis, which plays an essential role in coordinating HSC fatedecisions during regenerative stress and aging."

MERTK • SIGLEC1

Endothelial cell-derived thrombospondin-1 negatively affects hematopoietic function during aging (ASH 2025) - "5-fluorouracil (5-FU) sub-lethal myelosuppression on our Thbs1-GFP reporter showeddynamic Thbs1 expression throughout recovery within BM cells, indicating a possible cell-specific roleThbs1 plays during recovery...Other cell-specific models are currently being tested, and transplantation experiments areongoing. Collectively, we show that EC-derived Thbs1 plays a crucial role in the aging of the BM niche andrecovery post myelosuppressive treatment, validating it as a potential therapeutic target to support theregeneration of the hematopoietic system following myelosuppression in aged patients facingmalignancy."

Cardiovascular • Hematological Malignancies • THBS1

Azin1/tecr reprograms fatty acid metabolism to drive Acute Myeloid Leukemia progression (ASH 2025) - "Weobserved that there was no significant impact on steady stable hematopoiesis when Azin1 deletion.However, under stress conditions—including competitive repopulation assays, 5-fluorouracil (5-FU)challenge, and irradiation—Azin1 deficiency markedly impaired hematopoietic reconstitution potentialand reduced HSC self-renewal capacity...These results indicated that Azin1 stabilizes TECR to regulate AML by promotingfatty acid chain elongation.In summary, our study defines a non-polyamine axis which Azin1 stabilizes TECR to reprogram fatty acidmetabolism, fueling AML progression via TECR-ERK1/2/NF-κB axis. Pharmacological or genetic inhibitionof Azin1 offers a novel precision intervention strategy for AML by targeting its metabolic vulnerabilities."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Metabolic Disorders

Macrophage subsets provide distinct niches for normal and clonal hematopoiesis (ASH 2025) - "To assess thefunctional roles, we challenged mice with 5-fluorouracil (5FU) to trigger RBC clearance in the BM (ZhangD, Cell Stem Cell 2022), and observed phagocytic events only in R1, suggesting that R1 cells are bona fidemacrophages in the BM...By contrast, myeloid progenitors were localized in close proximity to theCD163- subset, and the distances were further reduced in PU.1-URE-/- mice. Collectively, our data suggestthat macrophage subsets in the BM provide distinct niches that support diverse hematopoietic processesin steady state and clonal diseases."

Hematological Malignancies • Myelodysplastic Syndrome • CCR2 • CD163 • CX3CR1 • HMOX1 • MERTK

PPM1D mutations confer resistance to venetoclax in pre-leukemic and AML populations (ASH 2025) - "In long-term co-culture assays,PPM1Dmut cells were competitively enriched, compared to WT cells upon exposure to eitherchemotherapy (Ara-C or 5-FU) or VEN...VEN combined with either small molecule PPM1D (GSK-2830371) or MDM2inhibitors (RG-7388) showed promising efficacy against PPM1Dmut, but were ineffective against TP53KOcells. In contrast, VEN + MCL1 inhibitor (S63845) was highly cytotoxic and efficacious across all genotypestested, including both PPM1Dmut and TP53KO cells...PPM1Dmutlikely arises in pre-leukemic or leukemic cells selected toexpand during VEN exposure. Resistance to VEN mediated by PPM1D abnormalities appeared to be TP53dependent and alleviated by combining VEN with MCL1 inhibition, which may also have clinical rationalein pts harboring concurrent PPM1D and TP53 mutant disease."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • FLT3 • KRAS • PPM1D • PTPN11

Overall survival (OS) in patients with metastatic colorectal cancer (mCRC) following persistent chemotherapy-induced thrombocytopenia (pCIT) (ASH 2025) - "pCIT was defined as the first occurrence of a platelet countmeasurement ≤85×109/L, ≥13 days after the nearest prior chemotherapy administration with fluorouraciland oxaliplatin (FOLFOX) or fluorouracil, irinotecan, and oxaliplatin (FOLFOXIRI); or ≥ 20 days afteroxaliplatin and capecitabine (CAPOX)... The median OS for mCRC patients following the first pCIT ranges from 9.7 to 23.5 months,with 6-month survival probabilities between 64% and 90%, across different LOTs. Multiple factors, suchas LOT, ECOG, age, CIT grade, and bevacizumab use, are associated with clinically relevant differences insurvival in patients with pCIT. These findings provide clinically relevant benchmarks for survival and maybe useful in assessing the need for supportive therapy."

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor • Thrombocytopenia

HX03 From pharaohs to fluorouracil: the enduring mystery of keloids. (PubMed, Br J Dermatol) - "Despite significant advancements, keloids continue to present a challenging clinical problem. Their unique occurrence in humans, particularly in those of African descent, and their relentless invasion into healthy skin make them a persistent enigma in modern medicine."

Journal • Dermatology • Fibrosis • Gastroenterology • Immunology • Oncology

Total Neoadjuvant Chemotherapy Followed by Laparoscopic Radical Gastrectomy Versus Neoadjuvant Chemotherapy for Clinical Stage T4a-bN + M0 Proximal Gastric Cancer: A Single-Center Retrospective Data Analysis. (PubMed, Gastroenterol Res Pract) - "Retrospective analysis was conducted on the clinical data of patients diagnosed with proximal LAGC who underwent perioperative docetaxel, oxaliplatin, and fluorouracil (FLOT) chemotherapy followed by laparoscopic radical gastrectomy at Longyan First Hospital affiliated with Fujian Medical University. The TNT approach for LAGC had the potential to enhance tumor regression and increase the completion rate of chemotherapy. This strategy demonstrated a positive trend in long-term outcomes and introduced a novel treatment model."

Journal • Retrospective data • Gastric Cancer • Oncology • Solid Tumor