Oral cancer, largely oral squamous cell carcinoma (OSCC), is a global health problem afflicting close to 300,000 people each year. Despite significant advances in surgical procedures and treatment, the long-term prognosis for patients with OSCC remains poor, with a 5-year survival rate at approximately 50% which is among the lowest for all major cancers. High mortality associated with OSCC is often attributed to the advanced disease stage of many OSCCs upon initial identification and surgical biopsy, underscoring the need for new diagnostic methods targeting early tumor progression and malignant transformations. We propose here a broad, innovative, high impact and cross-cutting translational research program that targets development, testing and validation of powerful new microchip sensor systems for the diagnosis, prognosis and monitoring of potentially malignant lesions (PML) and malignant lesions of the oral cavity. This effort pairs the leading group involved in development of nano-bio-chip systems with leading clinicians in pathology and oral cancer research. To support the testing and validation of the new microchip sensor systems, subjects will be recruited that are diagnosed clinically with a suspicious, potentially malignant (provisional clinical diagnosis of leukoplakia or erythroplakia) or oral squamous cell carcinoma, where a conventional biopsy is indicated. The programmable nano-bio-chip (PNBC) to be developed through this program will allow for the analysis of cellular samples obtained from a minimally invasive brush biopsy sample. The cell suspensions collected in this manner will allow for the simultaneous quantification of cell morphometric data and expression of molecular biomarkers of malignant potential in an automated manner using refined image analysis algorithms based on pattern recognition techniques and advanced statistical methods. This novel PNBC approach, which will turn around biopsy results in a matter of minutes as compared to days for traditional pathology methods, has already demonstrated its ability to distinguish between normal mucosa and oral cancer lesions. We propose here to adapt this chip-based platform to include a panel of biomarkers indicative of dysplasia as derived from cytomorphometric and molecular data as well as to assess the capabilities of this approach to function in point of care settings using noninvasive brush biopsy samples. The PNBC approach will be compared to the current standard of care based on biopsy and histopathological assessment of the lesions. The multi-institution, multi-disciplinary team assembled with members from Rice University, the Universities of Texas Health Science Centers in Houston and San Antonio, and the University of Sheffield, offers unique patient based case/control resources, biomarker and pathology proficiency combined with the expertise in integrated microchip sensors that will allow the team to develop new diagnostic aids for oral cancer patients that are desperately needed.

Public Health Relevance

Despite significant advances in surgical procedures and treatment, the long-term prognosis for patients with oral cancer remains among the lowest for all major cancers. In contrast, if detected early, the prognosis for oral cancer patients is excellent with more than 90% five-year survival. We propose the development of a minimally-invasive brush biopsy test for oral cancer diagnosis (no scalpel biopsy would be required) that when combined with a novel microchip can be performed in clinics or dentist's offices with results that are available in a matter of minutes (within visit) versus hours for scalpel biopsies. This """"""""pathology on a chip method"""""""" could facilitate regular monitoring of patients at risk of developing oral cancer as well as those receiving treatment. The new methods are projected to benefit greatly both patients and clinicians, while at the same time lowering associated healthcare costs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
High Impact Research and Research Infrastructure Programs (RC2)
Project #
5RC2DE020785-02
Application #
7939647
Study Section
Special Emphasis Panel (ZDE1-MH (38))
Program Officer
Burgoon, Penny W
Project Start
2009-09-25
Project End
2013-09-30
Budget Start
2010-09-01
Budget End
2013-09-30
Support Year
2
Fiscal Year
2010
Total Cost
$943,604
Indirect Cost
Name
Rice University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
050299031
City
Houston
State
TX
Country
United States
Zip Code
77005
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