Development of Diagnostic Tools for Metastatic Melanoma via Imaging of Heparanase Activity
Abstract
Principal Investigator’s Career Goal: This research directly addresses the following Peer Reviewed Cancer Research Program topic area -- “Melanoma and other skin cancers” and Military Relevance Focus Area -- “gaps in cancer research that impact the health of military beneficiaries,” more specifically, “development of new molecular imaging approaches for the early detection of aggressive melanoma.” This award will help me establish as a successful melanoma researcher. My mentors are internationally well-known cancer researchers, and they have developed career development plan with me to help me develop into a successful independent cancer researcher. Applicability of the Research: Melanoma is the most lethal skin cancer, mainly due to the high tendency for early metastasis. Although there is a high overall 10-year survival rate for patients whose melanoma is detected early, the survival rate drops to less than 10% once metastasis occurs (American Cancer Society). It is estimated that around 10,000 people in the U.S. will die of melanoma in 2015. Therefore, detection of the metastatic potential of melanoma and development of therapeutics to intervene the metastasis are key to improving the prognosis of melanoma patients. However, early melanoma can be overlooked because harmless moles and early melanoma tumors can look similar under the microscope, which is commonly used by pathologists for melanoma diagnosis. Therefore, new diagnostic techniques are highly demanded in the diagnosis of melanoma. Better and earlier diagnosis is particularly needed for individuals who have excessive exposure to the ultraviolet radiation from the sun. Hence, there is an extremely urgent need for the development of imaging agents or methodologies for early detection of malignant melanoma, especially that with high metastatic potential. We propose to develop a positron emission tomography (PET) imaging probe for heparanase, and we hope through imaging its activity we can detect “invisible” but aggressive cancer lesions. Heparanase is an enzyme overexpressed in melanoma; it promotes cancer cell growth and is extremely active in cancer tissue with metastatic potential. It is the major player to initiate metastasis by disseminating cancer cells so that they can migrate to distant organs/sites. Therefore, imaging the activity of heparanase is a highly promising approach to detect cancer at a molecular level, most importantly, before metastasis occurs. The lack of such agents stimulates our desire to develop highly specific and highly sensitive imaging probes for heparanase. Melanoma patients will benefit directly from our research, as our proposed imaging probe detect will metastatic potential of melanoma at a molecular level, therefore providing high accuracy and greater sensitivity than the conventional screening (morphological change under microscope), and it is non-invasive. These medical imaging probes can be applicable to human patients provided that the preclinical evaluation of the PET probes in animal models (established in this current proposal) is successful. These probes can detect metastatic melanoma non-invasively in patients while providing full-body scan to find otherwise invisible cancerous lesions in addition to visible malignant moles. The projected time to finish the current proposal is 3 years, and we can then be sure whether these molecular probes are suitable for human melanoma diagnosis. Diagnosis of melanoma early enough (at Stage I or II) before the cancer cells spread to other organs can almost guarantee a 100% cure rate upon surgical removal of the primary melanoma. Therefore, our research is aligned with early detection of melanoma; more specifically, our probes are designed to tell how aggressive the melanoma cells are/will be; therefore, they can provide more accurate alert signs for both doctors and patients. Early detection of melanoma can greatly improve the survival rate, prognosis and li
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710529
Entities
People
- Lina Cui
Organizations
- United States Army
- University of New Mexico