We intend to devise a novel therapeutic strategy based on a specific cancer cell receptor named EphA2, which is abundant on the surface of metastatic pancreatic cancers. Over the past several years our studies focused on testing the anti-cancer potential of agents targeting the receptor in suppressing cell migration and invasion in cellular studies, as well as in inhibiting tumor metastases using in vivo models. Very recently we have derived the most effective agonistic agent reported to date that potently targets the EphA2 receptor and causes its degradation. In preliminary studies, the agent is remarkably effective in inhibiting pancreatic cancer cell migration. The agent also causes the internalization of the receptor; hence we intend to probe whether we can use this agent also to deliver chemotherapy selectively to pancreatic tumors.
Public Health Relevance Statement: PROJECT NARRATIVE We propose to target a specific tumor marker, EphA2, expressed on the surface of aggressive pancreatic cancers. We propose to develop our potent and effective EphA2 targeting agent, Targefrin, that effectively inhibits tumor metastases. We will also probe Targefrin as an effective drug deliver agent to target chemotherapy selectively to the tumor and circulating cancer cells. Hence the proposed therapeutic strategy would simultaneously eliminate the primary tumor and suppress pancreatic cancer metastases.
Project Terms: 21+ years old; Adult Human; adulthood; Adult; Albumins; Azoles; Biopsy; Breast; Malignant Neoplasms; Cancers; Malignant Tumor; malignancy; neoplasm/cancer; Cell Line; CellLine; Strains Cell Lines; cultured cell line; cell motility; Cell Locomotion; Cell Migration; Cell Movement; Cellular Migration; Cellular Motility; Motility; Clinical Research; Clinical Study; Clinical Trials; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Esters; Future; Ligands; Names; name; named; naming; Neoplasm Metastasis; Metastasis; Metastasize; Metastatic Lesion; Metastatic Mass; Metastatic Neoplasm; Metastatic Tumor; Secondary Neoplasm; Secondary Tumor; cancer metastasis; tumor cell metastasis; Pancreas; Pancreatic; pancreatic neoplasm; Pancreas Neoplasms; Pancreas Tumor; Pancreatic Tumor; pancreatic neoplasia; Patients; Prostate; Prostate Gland; Prostatic Gland; Research Personnel; Investigators; Researchers; Signal Transduction; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Testing; Tissues; Body Tissues; Tumor Markers; TM-MKR; tumor biomarker; tumor specific biomarker; gemcitabine; Difluorodeoxycytidine; dFdC; dFdCyd; Anzatax; Asotax; Bristaxol; Paclitaxel (Taxol); Praxel; Taxol; Taxol A; Taxol Konzentrat; Paclitaxel; Surrogate End Points; Surrogate Endpoint; Organ; Site; Surface; Clinical; Penetration; Phase; PTK Receptors; Receptor Tyrosine Kinase Gene; Transmembrane Receptor Protein Tyrosine Kinase; Tyrosine Kinase Linked Receptors; Tyrosine Kinase Receptors; Receptor Protein-Tyrosine Kinases; Link; Evaluation; Blood Serum; Serum; Measurement; Patient Selection; Oncologist; Solid Tumor; Solid Neoplasm; Letters; Therapeutic; Cytotoxic drug; Cytotoxic agent; Normal tissue morphology; Normal Tissue; cancer cell; Malignant Cell; Malignant neoplasm of pancreas; Malignant Pancreatic Neoplasm; Pancreas Cancer; Pancreatic Cancer; pancreatic malignancy; Side; Protocols documentation; Protocol; neoplastic cell; Tumor Cell; receptor; Receptor Protein; receptor internalization; Toxic effect; Toxicities; Primary Neoplasm; Primary Tumor; novel; Reporting; chemotherapeutic agent; EphA2 Receptor; EphA2 Protein; EphA2 Receptor Tyrosine Kinase; EphA2-Tyrosine Kinase; Epithelial Cell Kinase Protein; Mammary-Derived Tyrosine Kinase 2; Property; End Point Assay; Endpoint Assays; circulating cancer cell; Investigational Therapies; Experimental Therapies; Investigational Treatments; experimental therapeutic agents; experimental therapeutics; Molecular Interaction; Binding; Dose; Affinity; Detection; Receptor Cell; in vivo; in vivo Model; Invaded; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Xenograft Model; xenograft transplant model; xenotransplant model; Development; developmental; Abraxane; designing; design; innovate; innovative; innovation; Oncogenic; chemotherapy; new diagnostics; next generation diagnostics; novel diagnostics; tumor; overexpress; overexpression; new therapeutic approach; new therapeutic intervention; new therapeutic strategies; new therapy approaches; new treatment approach; new treatment strategy; novel therapeutic approach; novel therapeutic strategies; novel therapy approach; novel therapeutic intervention; FDA approved; standard of care; pancreatic tumor cells; pancreatic cancer cells; Drug Targeting; imaging in vivo; in vivo imaging; targeted drug therapy; targeted drug treatments; targeted therapeutic; targeted therapeutic agents; targeted therapy; targeted treatment; targeted agent; Formulation; efficacy study; imaging study; first in man; first-in-human; anticancer; anti-cancer; pancreatic tumor model; pancreatic cancer model; Prognosis; diagnostic strategy; diagnostic approach; pharmacologic
