Arizona Cancer Therapeutics LLC (ACT) proposes a two-year, preclinical research project in cooperation with the University of Arizona Cancer Center to develop the novel anti-tumor therapeutic, Protein transduction domain-MUC1 Inhibitory Peptide (PMIP). PMIP is an intracellular MUC1 peptide that acts as a decoy to block the MUC1- oncoprotein interactions that drive breast cancer growth and metastasis. Utilizing a protein transduction domain to allow for transmembrane cellular uptake, PMIP can freely enter the cell and interact with intracellular target proteins. Laboratory research at the University of Arizona over the past nine years has examined the ability of MUC1 and an oncogenic partner, epidermal growth factor receptor (EGFR), to synergistically drive breast cancer progression. To block these tumor-specific, intracellular interactions, the first-in-class peptide-based cancer therapeutic, PMIP, was developed. Studies in tumor-bearing mouse models demonstrate that PMIP blocks tumor growth and metastasis and is nontoxic and tumor specific, making it an excellent anti-tumor drug candidate to carry forward through preclinical studies and clinical trials. Over 40,000 Americans die annually from metastatic breast cancer and, in greater than 90 percent of human breast carcinomas and metastases, MUC1 is over-expressed. This project represents critical steps in preclinical studies in drug dosing, absorption, distribution, metabolism and toxicity. The project will also investigate the benefits of PMIP when used in combination with FDA-approved chemotherapies for breast cancer. PMIP represents a unique approach to targeting MUC1 activities in cancer - other clinical trials targeting MUC1 have been designed to elicit anti-MUC1 immunity, and have been largely ineffective. Unlike these approaches, PMIP does not rely on activation of the immune response, but instead directly blocks tumor-promoting intracellular interactions. If successful, PMIP can substantially enhance the effective treatment options for metastatic breast cancer patients. This project aligns to NIH's mission to enhance health, lengthen life, and reduce the burdens of illness and disability by researching a new and unique anti-tumor drug to treat, effectively and with low or no toxicity, metastatic breast cancer.
Public Health Relevance Statement: Public Health Relevance: Arizona Cancer Therapeutics, LLC (ACT) proposes a two-year preclinical research project to develop a new anti-tumor drug, Protein transduction domain-MUC1 Inhibitory Peptide (PMIP). PMIP has been shown to block specific interactions inside cancer cells that drive tumor growth in metastatic breast cancer and has a high potential to substantially enhance treatment options for these patents. This project, by researching a new and unique anti-tumor drug to treat a cancer that results in 40,000 deaths in the U.S. annually, aligns to the National Institute of Health's mission to enhance health, lengthen life, and reduce the burdens of illness and disability.
NIH Spending Category: Biotechnology; Breast Cancer; Cancer; Orphan Drug; Rare Diseases
Project Terms: absorption; American; Animals; antitumor drug; Apoptosis; Arizona; Automobile Driving; base; Binding (Molecular Function); Biological Assay; Biotechnology; Breast Cancer Cell; Breast Cancer Treatment; Breast Carcinoma; burden of illness; cancer cell; Cancer cell line; Cancer Center; Cancer Patient; cell growth; Cells; Cessation of life; chemotherapy; Clinical Trials; combinatorial; Combined Modality Therapy; design; Development; disability; Disseminated Malignant Neoplasm; Docking; Dose; drug candidate; Drug Kinetics; effective therapy; Epidermal Growth Factor Receptor; Event; Experimental Designs; extracellular; FDA approved; Goals; good laboratory practice; Growth; Health; Human; Immune response; Immunity; Immunotherapy; improved; Investigational Drugs; Laboratory Research; Legal patent; Life; Lung Neoplasms; malignant breast neoplasm; Malignant neoplasm of lung; Malignant neoplasm of ovary; Malignant neoplasm of pancreas; Malignant Neoplasms; Metabolism; Metastatic Neoplasm to the Breast; Methods; Mission; Molecular; Mouse Mammary Tumor Virus; mouse model; Mucin-1 Staining Method; Mus; Neoplasm Metastasis; neoplastic cell; novel; novel strategies; novel therapeutics; Oncogene Proteins; Oncogenic; ovarian neoplasm; pancreatic neoplasm; patient population; Patients; Peptides; Pharmaceutical Preparations; Pharmacology; Pharmacology and Toxicology; Phase; Phase II Clinical Trials; pre-clinical; pre-clinical research; preclinical study; Property; Protein Analysis; protein profiling; protein protein interaction; Proteins; public health relevance; Publications; Publishing; Reporting; Research; Research Contracts; Research Project Grants; Therapeutic; therapeutic protein; therapeutic target; Toxic effect; Toxicology; Transgenic Mice; tumor; Tumor Expansion; tumor growth; tumor progression; United States National Institutes of Health; Universities; uptake; Vaccines; Work
