Inhibitor of differentiation (Id) genes and proteins play a significant role in tumor biology, and an anti-Id therapy in combination with a taxanes, a widely prescribed class of cytotoxic (paclitaxel/docetaxel, docetaxel or protein-bound paclitaxel) to treat cancer, is hypothesized to significantly improve the efficacy of the taxane without compromising safety while also providing additional anti-cancer activity. An effective Id1 inhibitor would potentially improve the efficacy of the taxanes by three distinct mechanisms: (i) preventing endothelial repair and thereby promoting the intrinsic anti-angiogenic effect of paclitaxel/docetaxel, (ii) lowering the anti-apoptotic environment of the tumor making it more susceptible to the cytotoxicity of paclitaxel/docetaxel and (iii) augmenting the cytotoxicity of paclitaxel/docetaxel by a direct anti-cancer effect. The goal of this proposal is to provide data to justify formal preclinical development and initial clinical evaluation of this therapeutic approach with an anti-Id1 small molecule. Experiments to be funded by the grant include xenograft studies in mice to establish the optimum dosing regimen for both the anti-Id agent and the taxanes. , ,
Public Health Relevance: Anti-microtubule taxanes like paclitaxel and docetaxel are widely prescribed cytotoxics to treat cancer. An effective Id1 inhibitor would potentially improve the efficacy of taxanes by three distinct mechanisms: (i) preventing endothelial repair and thereby promoting the intrinsic anti-angiogenic effect of taxanes, (ii) lowering the anti-apoptotic environment of the tumor making it more susceptible to the cytotoxicity of the taxanes, and (iii) augmenting the cytotoxicity of the taxanes by a direct anti-cancer effect. The goal of this proposal is to provide data to justify formal preclinical development and initial clinical evaluation of this therapeutic approach using an anti-Id1 small molecule.
Thesaurus Terms: Angiogenesis Antagonists;Angiogenesis Blockers;Angiogenesis Inhibitors;Angiogenetic Antagonists;Angiogenic Antagonists;Angiostatic Agents;Animals;Anti-Angiogenetic Agents;Anti-Angiogenic Agents;Anti-Angiogenic Drugs;Anti-Vegf;Anti-Vegf Humanized Monoclonal Antibody;Anti-Vegf Rhumab;Antiangiogenesis Agents;Antiangiogenic Agents;Anzatax;Apoptosis;Apoptosis Pathway;Apoptotic;Asotax;Athymic Nude Mouse;Bevacizumab (Rhumab Vegf);Bone Marrow;Bristaxol;Cancer Patient;Cancer Staging;Cancers;Cell Death, Programmed;Cells;Clinical;Clinical Evaluation;Clinical Testing;Complex;Data;Development;Diagnostic Neoplasm Staging;Differentiating Agents;Differentiation Agents;Differentiation Inducer;Differentiation Inhibitor;Differentiation Therapy;Dose;Drug Kinetics;Drugs;Endothelial Cells;Environment;Family;Fetal Development;Fetal Development Of The Mammalian Embryo Or Fetus;Funding;Gene Proteins;Genes;Goals;Grant;Hth Dna Binding Domain;Hth Motifs;Helix-Turn-Helix Motifs;Heterograft;Human;Human, General;Id Dna Binding Protein Inhibitor;Imatinib;Inhibitor Of Differentiation Proteins;Inhibitors, Angiogenetic;Inhibitors, Angiogenic;Life;Lytotoxicity;Malignant Neoplasms;Malignant Tumor;Mammals, Mice;Man (Taxonomy);Man, Modern;Medication;Metastasis;Metastasize;Metastatic Neoplasm;Metastatic Tumor;Mice;Mice, Athymic;Mice, Nude;Micro-Tubule;Microtubules;Moab Vegf;Monoclonal Antibody Anti-Vegf;Murine;Mus;N-Debenzoyl-N-(Tert-Butoxycarbonyl)-10-Deacetyltaxol;Neoplasm Metastasis;Neoplasm Staging;Neovascularization Inhibitors;Nude Mice;Outcome;Paclitaxel;Paclitaxel (Taxol);Patients;Pharmaceutic Preparations;Pharmaceutical Preparations;Pharmacokinetics;Phase;Phenotype;Play;Praxel;Protein Binding;Protein Gene Products;Proteins;Recombinant Humanized Anti-Vegf Monoclonal Antibody;Recombinant Humanized Monoclonal Antibody To Vascular Endothelial Growth Factor;Regimen;Relative;Relative (Related Person);Reticuloendothelial System, Bone Marrow;Rhumab Vegf;Role;Safety;Secondary Neoplasm;Secondary Tumor;Taxane Compound;Taxanes;Taxol;Taxol (Old Nsc);Taxol A;Taxol Konzentrat;Taxotere;Therapeutic;Therapeutic Index;Time;Transplantation, Heterologous;Tumor Biology;Tumor Cell Migration;Tumor Staging;Xenograft;Xenograft Procedure;Xenotransplantation;Angiogenesis;Antiangiogenic;Base;Bevacizumab;Cancer Metastasis;Clinical Test;Cytotoxic;Cytotoxicity;Docetaxel;Docetaxol;Drug/Agent;Experiment;Experimental Research;Experimental Study;Gene Product;Helix Loop Helix;Helix Turn Helix;Improved;Inhibitor;Inhibitor/Antagonist;Malignancy;Meetings;Migration;Neoplasm/Cancer;Pre-Clinical;Preclinical;Precursor Cell;Prevent;Preventing;Public Health Relevance;Repair;Repaired;Research Clinical Testing;Research Study;Response;Rhumabvegf;Senescence;Small Molecule;Social Role;Taxane;Tumor;Tumor Growth
