Accession Number : AD1049267


Title :   Targeting Neutrophil Protease-Mediated Degradation of Tsp-1 to Induce Metastatic Dormancy


Descriptive Note : Technical Report,30 Sep 2016,29 Sep 2017


Corporate Author : Weill Medical College of Cornell University New York United States


Personal Author(s) : Mittal, Vivek


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1049267.pdf


Report Date : 01 Oct 2017


Pagination or Media Count : 11


Abstract : External pre-existing inflammation in the lungs is linked to increased incidence of metastasis. Inflammation-mediated by bacterial infection or cigarette smoke enhanced pulmonary metastasis from breast cancer in humans and mice. Similarly, autoimmune arthritis, characterized by increased recruitment of inflammatory neutrophils and macrophages in the lungs was associated with increased breast cancer metastasis to the lungs. Despite this compelling link between inflammation and metastasis, the mechanisms by which inflammation contributes to tumor outgrowth in distant metastatic organs have remained underexplored. We believe that targeting inflammation-mediated metastasis has tremendous potential in the treatment of high-risk breast cancer patients. Overarching challenges. Breast cancer affects more than 1.7 million individuals a year worldwide, with approximately 500,000 deaths. Importantly, 90% of this mortality is a consequence of metastatic disease that is resistant to adjuvant therapies. Despite this clinical significance, there is a conspicuous lack of a single FDA approved molecularly targeted anti-metastatic therapy. Hence, there is an urgent medical need to develop new targeted anti-metastatic therapeutic approaches. However, a lack of mechanistic understanding by which tumor cell colonize and outgrow in distant metastatic organs, has been a major impediment to the development of an effective anti-metastatic therapy. Hypothesis /Objective. We hypothesize that intervention against inflammation-driven neutrophil elastase (NE)/Cathepsin G (CG)-Thrombospondin-1 (Tsp-1) axis can be developed into an anti-metastatic therapy in breast cancer.


Descriptors :   breast cancer , metastasis , lipopolysaccharides , bone marrow , inflammation lung cancer , macrophages , neoplasms , inhibition , peptides


Subject Categories : Medicine and Medical Research
      Anatomy and Physiology
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE