Tomudex (raltitrexed) / Pfizer, AstraZeneca 
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  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Journal, Heterogeneity:  Single-Cell Chemical Proteomics (SCCP) Interrogates the Timing and Heterogeneity of Cancer Cell Commitment to Death. (Pubmed Central) -  Jul 9, 2022   
    Using SCCP, we studied here the time-resolved response of individual adenocarcinoma A549 cells to anticancer drugs methotrexate, camptothecin, and tomudex, revealing the early emergence of cellular subpopulations committed and uncommitted to death. As a novel and useful approach to exploring the heterogeneous response to drugs of cancer cells, SCCP may prove to be a breakthrough application for single-cell proteomics.
  • ||||||||||  5-fluorouracil / Generic mfg., oxaliplatin / Generic mfg., leucovorin calcium / Generic mfg.
    Enrollment open, Metastases:  Hepatic Arterial Infusion of Raltetrexed With Oxaliplatin(SALOX) Versus FOLFOX in Advanced Hepatocellular Carcinoma (clinicaltrials.gov) -  May 23, 2022   
    P3,  N=426, Recruiting, 
    Importantly, this is the first research comparing the two treatments, and we believe that the results of this article could present a primary choice for clinical doctors dealing with patients with standard treatments that failed mCRC. Not yet recruiting --> Recruiting
  • ||||||||||  Zolinza (vorinostat) / Merck (MSD), Tomudex (raltitrexed) / Pfizer, AstraZeneca, entinostat (SNDX-275) / Kyowa Kirin, Syndax Pharma
    Journal, Combination therapy:  Effect of Uracil DNA Glycosylase Activity on the Efficacy of Thymidylate Synthase Inhibitor/HDAC Inhibitor Combination Therapies in Colon Cancer. (Pubmed Central) -  May 14, 2022   
    Interestingly, UNG2 protein levels can also be depleted by the HDAC inhibitors SAHA and MS275, providing a pharmacologic strategy to reduce UNG2 activity in cells...Our combined genetic and pharmacologic strategies targeting UNG2 activity in cells are defining cell death mechanisms for combination therapies of TS inhibitors and HDAC inhibitors. Future work will examine these drug combinations in additional cell lines to understand optimal therapeutic combinations and to further refine mechanisms of cell death.
  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Preliminary results of raltitrexed in Chinese patients with metastatic colorectal cancer: A prospective, multicenter, real-world study. (Available On Demand; 385) -  Apr 28, 2022 - Abstract #ASCO2022ASCO_1392;    
    Between May 2018 and December 2021,a total of 1039 patients from 57 centers were screened for enrollment,among which 271 patients were treated with raltitrexed plus irinotecan, 753 patients accepted target therapy (bevacizumab or cetuximab) additionally, and 15 patients combined with other drugs. The real-world study confirmd that raltitrexed was an effective and safe regimen for the second-line treatment in Chinese patients with mCRC, especially combined with target therapy additionally, which was aligned with previous trials.
  • ||||||||||  methotrexate / Generic mfg., sirolimus / Generic mfg.
    Journal:  Precipitate-Supported Thermal Proteome Profiling Coupled with Deep Learning for Comprehensive Screening of Drug Target Proteins. (Pubmed Central) -  Feb 19, 2022   
    Using a promiscuous kinase inhibitor, staurosporine, we delineated 99 kinase targets with a specificity up to 83% in K562 cell lysates, which represented a significant improvement over the existing thermal shift methods. Furthermore, the PSTPP strategy was successfully applied to analyze the binding targets of rapamycin, identifying the well-known targets, FKBP1A, as well as revealing a few other potential targets.
  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Journal:  Thymidylate synthase is essential for efficient HIV-1 replication in macrophages. (Pubmed Central) -  Dec 25, 2021   
    Indeed, a TS specific small interfering RNA (siRNA) as well as the TS specific inhibitor Raltitrexed (RTX) caused a reduction in productively infected cells...These results suggest that TS is essential for the early stages of HIV-1 infection by providing optimal dNTP concentrations in MDMs. TS and its related pathway may thus be considered as a potential therapeutic target for HIV-1 treatment.
  • ||||||||||  Teysuno (gimeracil/oteracil/tegafur) / Nordic Group, Otsuka, Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Clinical, P2 data, Journal:  A prospective phase II study of raltitrexed combined with S-1 as salvage treatment for patients with refractory metastatic colorectal cancer. (Pubmed Central) -  Dec 1, 2021   
    P2
    Raltitrexed in patients with colorectal cancer who were previously treated with fluoropyrimidine-based systemic therapy is effective and well-tolerated. The RS regimen demonstrated favorable effects in patients with mCRC following failure of standard chemotherapy, and could be a new choice for third-line treatment, and must be verified in future randomized clinical trials (Clinical trial: NCT02618356).
  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Preclinical, Journal:  An In Vitro Comparative Study of Three Drug-Eluting Beads Loaded with Raltitrexed. (Pubmed Central) -  Nov 17, 2021   
    The amount of drug loading could meet clinical requirements by the optimized method. All three raltitrexed-loaded DEBs showed poor compatible stability with iopamidol, as well as rapid drug release performance, which should be noticed in clinical practice.
  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca, Fruzaqla (fruquintinib) / Takeda
    Enrollment open, Monotherapy, Metastases:  Fruquintinib and Raltitrexed Versus Fruquintinib Monotherapy in Advanced Colorectal Cancer (clinicaltrials.gov) -  Oct 26, 2021   
    P2,  N=136, Recruiting, 
    All three raltitrexed-loaded DEBs showed poor compatible stability with iopamidol, as well as rapid drug release performance, which should be noticed in clinical practice. Not yet recruiting --> Recruiting
  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Trial completion, Trial completion date, Trial primary completion date, Metastases:  Preoperative Chemoradiotherapy With Raltitrexed for Intermediate or Locally Advanced Rectal Cancer in the Fit Elderly (clinicaltrials.gov) -  Sep 9, 2021   
    P2,  N=68, Completed, 
    DEB-TACE loaded with epirubicin and raltitrexed improves the short-term outcomes, reduces the tumor load, decreases the incidence of adverse events, and improves the survival rate in patients with intermediate and advanced PHC. Recruiting --> Completed | Trial completion date: Sep 2022 --> Aug 2021 | Trial primary completion date: Sep 2019 --> May 2021
  • ||||||||||  Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Journal:  Tumor acid microenvironment-activated self-targeting & splitting gold nanoassembly for tumor chemo-radiotherapy. (Pubmed Central) -  Sep 2, 2021   
    Polyethylene glycol linked raltitrexed (RTX, target ligand and chemotherapy drug) and two tertiary amine molecules (1-(2-aminoethyl) pyrrolidine and N, N-dibutylethylenediamine) are modified on the surface of the 6-nm gold nanoparticles by lipoic acid to form gold nanoassembly defined as Au-NNP(RTX)...Meanwhile, after disassembly, more RTXs on the surface of gold nanoparticles are exposed from the shielded state of assembly along with 2.25-fold augment of cellular uptake capability. Most importantly, the results show that Au-NNP(RTX) possesses of high tumor accumulation and effective tumor penetration, thereby enhancing the tumor chemo-radiotherapy efficiency.
  • ||||||||||  Avastin (bevacizumab) / Roche, Tomudex (raltitrexed) / Pfizer, AstraZeneca
    Trial completion date, Trial primary completion date, Metastases:  Raltitrexed-based Chemotherapy Plus Bevacizumab in Retreated Patients With Advanced Colorectal Cancer (clinicaltrials.gov) -  Aug 30, 2021   
    P2,  N=100, Recruiting, 
    Most importantly, the results show that Au-NNP(RTX) possesses of high tumor accumulation and effective tumor penetration, thereby enhancing the tumor chemo-radiotherapy efficiency. Trial completion date: Feb 2020 --> Feb 2023 | Trial primary completion date: Aug 2018 --> Aug 2022
  • ||||||||||  Preclinical, Journal:  Anticancer Drugs for Intra-Arterial Treatment of Colorectal Cancer Liver Metastases: In-Vitro Screening after Short Exposure Time. (Pubmed Central) -  Aug 7, 2021   
    The aim of this study was to select the most efficient drug on a panel of colorectal cancer (CRC) cell lines (Caco-2, HCT 116, HT 29, SW 48, SW 480, SW 620) exposed for 30 min to 12 cytotoxic agents (doxorubicin, epirubicin, idarubicin, 5-FU, raltitrexed, gemcitabine, cisplatin, oxaliplatin, mitomycin C, irinotecan, streptozocin, paclitaxel) at different concentrations...Gemcitabine seemed to be the most efficient chemotherapy for SW48. Interestingly, the most commonly used cytotoxic agents in the systemic and intra-arterial treatment of colorectal liver metastasis (CRLM) (oxaliplatin, 5-FU, irinotecan) showed very limited cytotoxicity to all the cell lines.
  • ||||||||||  methotrexate / Generic mfg.
    Journal:  Initial Stages of Spontaneous Binding of Folate-Based Vectors to Folate Receptor-α Observed by Unbiased Molecular Dynamics. (Pubmed Central) -  Aug 6, 2021   
    Only folate, 5-methyltetrahydrofolate, and raltitrexed bind selectively at the active site of the receptor...Pemetrexed adsorbs nonspecifically on the protein surface, while methotrexate and pteroyl ornithine couple much less to the receptor...Analysis of the interactions between the ligands and FRα shows that in order to accomplish specific binding to the active site, a combination of hydrogen bonding, π-stacking, and van der Waals and Coulomb attraction should be feasible simultaneously for the vector molecule. The reported results demonstrate that it is possible to observe receptor-ligand binding without applying bias by representing the local environment as close as possible and contain important molecular-level guidelines for the design of folate-based systems for targeted delivery of anticancer drugs.