Restricted Research - Award List, Note/Discussion Page
Fiscal Year: 2023
1771 The University of Texas at El Paso (143659)
Principal Investigator: Al-Hilal,Taslim A
Total Amount of Contract, Award, or Gift (Annual before 2011): $ 1,744,460
Exceeds $250,000 (Is it flagged?): Yes
Start and End Dates: 8/1/22 - 7/31/27
Restricted Research: YES
Academic Discipline: Pharmaceutical Science
Department, Center, School, or Institute: Pharmaceutical Science
Title of Contract, Award, or Gift: Targeting of Doppel-axis to Control Lung Tumor Angiogenesis and Immunity
Name of Granting or Contracting Agency/Entity:
NIH - NATIONAL CANCER INSTITUTE
CFDA Link: HHS
93.395
Program Title:
Cancer Treatment Research
CFDA Linked: Cancer Treatment Research
Note:
Tumors, just like normal tissues, require blood vessels to receive nutrients and oxygen and to eliminate wastes and carbon dioxide. To ensure this blood supply, tumors create their own vascular beds from established blood vessels by a process called angiogenesis. This process plays a major role in tumor growth, survival, and invasiveness. Currently, various monoclonal antibodies (mAb) and small-molecular-weight drugs are used to restrain angiogenesis and starve tumors of nutrients. However, angiogenesis not only drives the growth of blood vessels in tumors, it also performs many important physiological functions in the body. The 'good' (physiological) angiogenesis regulates the thrombotic process, maintains vascular tone, and speeds up wound healing. Unfortunately, current anti-angiogenic drugs indiscriminately inhibit both good and 'bad' (tumor-directed) angiogenesis. In principle, it should be possible to reduce or eliminate many of the side effects of current anti-angiogenic drugs by blocking signaling molecules that are expressed only in tumor endothelial cells (TECs) but not in normal endothelial cells (NECs). Recently, we discovered that a prion-like protein called doppel is expressed only in TECs but not in NECs. Thus, we posit that doppel is a new pro-angiogenic factor in tumor, genetic deletion of doppel arrests neoangiogenesis during tumor progression, and therapeutic targeting of doppel not only eliminate tumor but also reduce off-tumor effects. The proposed TEC-specific anti-angiogenic agent is likely to emerge as a far superior and safer alternative to current anti-angiogenic drugs because we will explore its relation to new signaling pathways that independent of VEGFR2 or receptor tyrosine kinases.
Discussion: No discussion notes