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  • ||||||||||  PF-04136309 / Pfizer
    Determination of permissive and restraining cancer-associated fibroblast (DeCAF) subtypes (Section 36) -  Mar 5, 2024 - Abstract #AACR2024AACR_7555;    
    P1
    Analysis of a phase Ib trial FOLFIRINOX in combination with a CCR2 inhibitor (PF-04136309; NCT01413022) , we found that in patients with classical tumors, increasing permCAF probability was associated with response (r = -0.688, p<0.001)...DeCAF subtypes are associated with histological subtype in MESO (p = 0.021) and grade in KIRC (p = 0.056). Taken together, DeCAF subtypes explain the role of CAF subtypes in patients, provide a foundation for the translation of preclinical studies, and facilitate the design of future therapeutic approaches and clinical trials.
  • ||||||||||  Hyleukin-7 (efineptakin alfa) / Genexine, NeoImmuneTech
    rhIL-7-hyFc (efineptakin-alfa, NT-I7) increases tumor-specific CD8+ T cells despite FOLFOX cytotoxicity effect (Section 4) -  Mar 5, 2024 - Abstract #AACR2024AACR_7009;    
    However, adding FOLFOX does not affect the NT-I7-driven increase of tumor-specific CD8+ T cells within the tumor. Taken together, our data demonstrate that FOLFOX does not compromise NT-I7's ability to increase tumor-specific T cells within the tumor and the combination enhances the anti-tumor response irrespective of the timing of NT-I7 administration.
  • ||||||||||  5-fluorouracil / Generic mfg., leucovorin calcium / Generic mfg., irinotecan / Generic mfg.
    Combination of FOLFIRI (5-FU, Leucovorin, and Irinotecan) and ProAgio on colon cancer growth and metastasis (Section 23) -  Mar 5, 2024 - Abstract #AACR2024AACR_6727;    
    Taken together, our data demonstrate that FOLFOX does not compromise NT-I7's ability to increase tumor-specific T cells within the tumor and the combination enhances the anti-tumor response irrespective of the timing of NT-I7 administration. Our study offers encouraging observations that ProAgio plus FOLFIRI can suppress colon cancer growth and metastasis by inhibiting ?v?3 preclinically and may provide a novel therapeutic combination for the management of colon cancers.
  • ||||||||||  5-fluorouracil / Generic mfg.
    Comparative studies of chemotherapy and immuno-oncology combinations in multiple mouse syngeneic tumor models (Section 42) -  Mar 5, 2024 - Abstract #AACR2024AACR_6554;    
    Specifically, we observed that the SOC/ICI combinations resulted in enhanced antitumor activities compared to single-agent treatments in many of the models. These data, particularly specific SoC combination regimens that combine well with ICIs in each disease, are useful for optimizing promising combination approaches for clinical development and will be presented here.
  • ||||||||||  STC-1010 / Brenus Pharma
    Efficacy of the STC-1010 a new allogenic cancer vaccine in different colorectal cancer models (Section 39) -  Mar 5, 2024 - Abstract #AACR2024AACR_6526;    
    In addition, mSTC-1010 associated with immunostimulant (cyclophosphamide and mGM-CSF), combined or not with chemotherapy (FOLFOX or FOLFIRI) led to a significant decrease of tumor volume, a M1-oriented macrophage response (immunohistochemical, iNOS/CD163 >1), and an increase of T lymphocyte infiltration...The good tolerability and reproducible efficiency of the STC-1010 vaccine in these different clinical models allow to plan a first-in-human phase I/II clinical trial for metastatic CRC(mCRC) patients. A dose-escalation and cohort extension phase I followed by a phase IIa with STC-1010 plus immunostimulant, associated to mFOLFOX6 w/o bevacizumab, will be performed for MSS mCRC patients to evaluate the safety and preliminary effectiveness in human.
  • ||||||||||  Organoids to predict treatment response in metastatic colorectal cancer (OPTIC) (Section 45) -  Mar 5, 2024 - Abstract #AACR2024AACR_6462;    
    OPTIC will enhance the clinical application of PDOs by defining thresholds for PDO sensitivity and analyzing the diagnostic power for different treatments. To enable personalized treatment in clinical practice, PDO screening should guide mCRC treatment and result in enhanced chance of response and reduced over- and mistreatment.
  • ||||||||||  L-pampo / CHA Vaccine Institute
    L-pampo (Section 28) -  Mar 5, 2024 - Abstract #AACR2024AACR_5479;    
    To compare the anti-tumor efficacy of L-pampo and conventional cytotoxic chemotherapy, we treated tumor-bearing mice with FOLFOX or paclitaxel as SoC regimen, respectively... This study suggests that L-pampo, a novel TLR2/3 agonist, can be a potent anti-tumor agent, improving the anti-tumor efficacy of ICIs in cold tumors with enhanced anti-tumor immunity and minimal toxicities than conventional chemotherapies.
  • ||||||||||  5-fluorouracil / Generic mfg.
    Intestinal microbiome with chemotherapy response and RAS mutation in patients with advanced or metastatic colorectal cancer: a pilot, exploratory study (Section 45) -  Mar 5, 2024 - Abstract #AACR2024AACR_4966;    
    All patients were treated with first-line systemic therapy; FOLFOX (5-fluorouracil and oxaliplatin)-based (n=13) and FOLFIRI (5-fluorouracil and irinotecan)-based chemotherapy (n=2)...Regarding the association of intestinal microbiome with RAS mutation, Bray curtis and weighted unifrac analyses revealed significant differences in beta diversity; higher incidence of Faecalibacterium, Lactobacillus, Prevotella, Anaerofilum, and UCG-005 in the RAS-wild type mCRC, while Bacteroides, Collinsella, Holdemanella, and Anaerostipes in RAS-mutated mCRC.This pilot study suggests the prognostic value of gut microbiomes and its association with RAS mutation in patients with mCRC treated with first line systemic therapy. A microbial functional study with immune cytokine change is planned to confirm these findings in future.
  • ||||||||||  Drug-induced cancer cell secretome promotes resistance in colon cancer (Section 26) -  Mar 5, 2024 - Abstract #AACR2024AACR_3989;    
    Additionally, in zebrafish xenograft, we found that 5-FU-R colon cancer cells cultured with 5-FU-induced secretome showed higher tail-vein metastatic burden compared to the 5-FU-R cells cultured with DMSO-induced secretome. This provides a background to further study in detail the therapy-induced resistance as well as dormancy in colorectal cancer which will help to develop approaches to prevent or reverse chemoresistance in patients who receive systemic therapy for mCRC.
  • ||||||||||  KRAS co-mutational landscape dictates treatment outcomes in pancreatic cancer (PC) patients (Section 45) -  Mar 5, 2024 - Abstract #AACR2024AACR_3805;    
    This study provides insights into the genetic makeup of patients with KRAS mutations and how co-mutation with TP53 affects outcomes of SoC treatments. It highlights the need for comprehensive genetic profiling to make better therapy decisions.Table 1: Evaluation of KRAS mutational landscape in PC and its impact on treatment outcomes.
  • ||||||||||  5-fluorouracil / Generic mfg.
    Predictive biomarkers for neoadjuvant FLOT4 chemotherapy response in gastroesophageal cancer: Results of multi-omics approach (Section 44) -  Mar 5, 2024 - Abstract #AACR2024AACR_3670;    
    The identified genes and pathways may serve as potential biomarkers for predicting treatment outcomes.Future Directions: By the time of the conference, we anticipate including a more extensive patient cohort with complete response or no response to FLOT4, and comparative analyses with a FOLFOX treatment group. The integration of forthcoming WES, methylation, miRNA, and proteomics data will provide a more comprehensive molecular predictive model.
  • ||||||||||  Unlocking the potential of miRNA sequencing for early detection and monitoring of pancreatic cancer progression and recurrence (Section 35) -  Mar 5, 2024 - Abstract #AACR2024AACR_3510;    
    To identify biomarkers for PC progression, we developed from the Gemcitabine-sensitive MIA-PaCa-2 (MP2) cell line the Gemcitabine and FOLFIRINOX resistant MP2-GR cell line...The miRNA set was used to predict both PC progression after treatment, and recurrence. We are currently refining this data set to increase its predictive sensitivity and widen our patient data set comparison to further elucidate this approach in a clinical setting.
  • ||||||||||  Genetic ablation of microRNA-10b improves treatment outcomes in mouse models of pancreatic cancer (Section 19) -  Mar 5, 2024 - Abstract #AACR2024AACR_3002;    
    These unique features endow PDAC tumors with an array of innate resistance mechanisms against standard-of-care (SOC) chemotherapy: gemcitabine/nab-paclitaxel or FOLFIRINOX...Notably, we observed a more durable response in treated female KPC; Mir-10bKO animals (n = 4 ) compared to any other experimental group (n > 5). We are currently performing tissue and molecular analyses to identify direct target genes involved in chemoresistance and sex-specific modulation of treatment response.
  • ||||||||||  ompenaclid (RGX-202) / Inspirna, EMD Serono
    Anti-tumor efficacy of ompenaclid, a creatine transporter inhibitor, in KRAS mutant tumors, including NSCLC (Section 18) -  Mar 5, 2024 - Abstract #AACR2024AACR_2984;    
    Notably, and consistent with findings in CRC, efficacy in NSCLC was more robust in RAS mutant cancer models, relative to those bearing KRAS WT tumors. Metabolite analysis of the plasma of tumor-bearing mice at baseline revealed that mice harboring RAS mutant tumors had higher levels of p-creatine and lower levels of ATP, indicating that RAS mutant tumors utilize higher amounts of ATP, which may be converted to phosphocreatine by tumoral CKB, as confirmed by qPCR analysis.
  • ||||||||||  Recentin (cediranib) / AstraZeneca, Avastin (bevacizumab) / Roche
    Targeted proteomics and next-generation sequencing (NGS) for biomarker discovery in metastatic colorectal cancer (mCRC) (Section 39) -  Mar 5, 2024 - Abstract #AACR2024AACR_2474;    
    P2/3
    Our preliminary findings for this cohort indicate the benefit of the use of multi-modal methodologies to inform better strategies for patient stratification and precision medicine, though further assessment of proteogenomic characteristics is needed. This data may inform future clinical development and guide patient eligibility to clinical trials and possible treatment sequencing for ADCs.
  • ||||||||||  5-fluorouracil / Generic mfg., leucovorin calcium / Generic mfg., irinotecan / Generic mfg.
    Modulation of the MSS and MSI colorectal cancer immune microenvironment with FOLFOX and FOLFIRI -/+ anti-PD-1 immunotherapy (Section 47) -  Mar 5, 2024 - Abstract #AACR2024AACR_2437;    
    Most patients receive 5-FU (F) and folinic acid (FOL) combined with oxaliplatin (OX), irinotecan (IRI), or both (OXIRI)...These data point to a FOX-specific mechanism by which CD8+ T cell infiltration into MSS mCRC tumors is enhanced, but their activation is halted potentially by GM-CSF suppression and/or type 1 cDC depletion in the TME. These findings contribute to our understanding of the mechanisms of chemotherapy-dependent immune modulation and bring the field closer to harnessing these effects for therapeutic gain.
  • ||||||||||  Opdivo (nivolumab) / Ono Pharma, BMS
    Dissecting pancreatic cancer tumor-immune microenvironment crosstalk using spatial transcriptomics (Section 46) -  Mar 5, 2024 - Abstract #AACR2024AACR_2302;    
    P2
    This enables the discovery of novel immune response biomarkers and potential therapeutic avenues to target tumor and microenvironment interactions.Trial Registration: DF/HCC protocol 18-179: Losartan and Nivolumab in Combination With FOLFIRINOX and SBRT in Localized Pancreatic Cancer. NCT03563248Ethics Approval: All studies presented were approved by the Dana-Farber/Harvard Cancer Center IRB protocols 18-179.
  • ||||||||||  5-fluorouracil / Generic mfg.
    Journal:  Maintenance of the Branched-Chain Amino Acid transporter LAT1 Counteracts Myotube Atrophy following Chemotherapy. (Pubmed Central) -  Mar 4, 2024   
    However, RNAi-mediated depletion of NEdd4, the protein ligase responsible for ubiquitin-dependent degradation of LAT1, attenuated the effects of chemotherapy on BCAA concentrations, anabolic signaling, protein synthesis and myofibrillar protein abundance. Thus, if our findings are validated in preclinical models, interventions regulating muscle amino acid transporters might represent a promising strategy to treat cachexia.
  • ||||||||||  Oncorine (recombinant human adenovirus type 5) / Mergen Ltd.
    Enrollment open, Trial completion date, Trial primary completion date:  Recombinant Human Adenovirus Type 5 Plus HAIC of FOLFOX for Intrahepatic Cholangiocarcinoma (clinicaltrials.gov) -  Mar 3, 2024   
    P4,  N=66, Recruiting, 
    Not yet recruiting --> Recruiting | Initiation date: Nov 2023 --> Feb 2024 Not yet recruiting --> Recruiting | Trial completion date: Apr 2024 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2026
  • ||||||||||  M9140 / EMD Serono
    Enrollment change, Trial completion date, Trial primary completion date, Metastases:  Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors (PROCEADE-CRC-01) (clinicaltrials.gov) -  Mar 3, 2024   
    P1,  N=180, Recruiting, 
    Not yet recruiting --> Recruiting | Trial completion date: Apr 2024 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2026 N=31 --> 180 | Trial completion date: Nov 2023 --> May 2025 | Trial primary completion date: Nov 2023 --> Apr 2024