Project Grant R43DE033314

A POINT-OF-CARE SALIVARY CYTOKINE TEST FOR EARLY DETECTION OF ORAL CANCER - PROJECT SUMMARY / ABSTRACT ORAL CANCER IS THE 6TH MOST COMMON CANCER GLOBALLY WITH ~ 350,000 NEW CASES AND CLAIMING ~ 180,000 LIVES ANNUALLY. COMMON RISK FACTORS INCLUDE SMOKING AND ALCOHOL CONSUMPTION. HOWEVER, OTHER LOCAL HABITS, SUCH AS KHAT CHEWING, CAN CAUSE SIGNIFICANTLY HIGHER REGIONAL HIGHER PREVALENCE (UP TO 40% OF ALL CANCER CASES IN SOME ASIAN COUNTRIES). CURRENTLY, IDENTIFICATION AND DIAGNOSIS OF ORAL CANCER RELY ON VISUAL INSPECTION FOLLOWED BY BIOPSY AND HISTOPATHOLOGICAL ANALYSIS. THIS PROCEDURE IS LENGTHY, COSTLY AND OFTEN PRONE TO ERROR. AS A RESULT, ORAL CANCER TODAY IS OFTEN DIAGNOSED AT ADVANCED STAGES THAT HAVE POOR PROGNOSIS WITH A 5-YEAR SURVIVAL RATE HOVERING AROUND 50% FOR DECADES. EVEN FOR THOSE WHO HAVE BEEN CURED, THEY OFTEN FACE SEVERE MORBIDITIES, SUCH AS DISFIGUREMENT, SPEECH AND SWALLOWING DIFFICULTIES. HOWEVER, IF ORAL CANCER CAN BE DIAGNOSED EARLY AND ALLOWING EARLY INTERVENTION, SURVIVAL RATE CAN IMPROVE TO ~ 90%. TESTING FOR SALIVARY BIOMARKERS REPRESENTS A PROMISING APPROACH FOR SCREENING AND DIAGNOSING ORAL CANCER EARLIER, SINCE 1) SALIVA COLLECTION IS CONVENIENT AND CAN BE PERFORMED EVEN AT THE DENTIST'S OFFICE, AND 2) SALIVA IS CLOSEST TO THE PRIMARY SITE OF TUMOR DEVELOPMENT WHICH CAN CONTAIN MOLECULES INDICATIVE OF MALIGNANT TRANSFORMATION. HENCE, WITH APPROPRIATE BIOMARKERS, A SIMPLE SALIVA TEST CAN BE DEVELOPED AND DEPLOYED AT THE POINT-OF-CARE (POC, E.G., DENTIST'S OFFICE) FOR RAPID SCREENING AND EARLY IDENTIFICATION OF ORAL CANCER. RECENTLY, FROM A NUMBER OF CLINICAL STUDIES GLOBALLY, PRO-INFLAMMATORY CYTOKINES HAVE EMERGED AS PROMISING BIOMARKERS FOR SCREENING AND DIAGNOSING ORAL CANCER WITH GOOD SENSITIVITY AND SPECIFICITY. AMONG THESE CYTOKINES, IL-6 AND IL-8 HAVE SHOWN THE BEST PREDICTIVE POWER FOR ORAL CANCER. CURRENTLY, MEASUREMENT FOR IL-6 AND IL-8, AS WELL AS OTHER CYTOKINES, OFTEN REQUIRE TEDIOUS MANUAL ASSAYS OR DELICATE AUTOMATED SYSTEMS WHICH CAN BE BOTH TIME CONSUMING AND COSTLY. AS A RESULT, CURRENTLY, IT IS IMPRACTICAL TO SCREEN FOR ORAL CANCER VIA SALIVARY BIOMARKERS AT THE POC. BASED ON NEED AND CLINICAL VALUES, GLUCOSENTIENT (GSI) IS PROPOSING TO DEVELOP A POC SYSTEM FOR SCREENING ORAL CANCER BY MEASURING SALIVARY LEVELS OF RELEVANT PRO-INFLAMMATORY CYTOKINES. THE POC SYSTEM WILL BE BASED ON THE EXISTING BLOOD GLUCOSE METER (BGM) HARDWARE AND A DISPOSABLE MICROFLUIDIC CARTRIDGE. TODAY'S BGM IS THE CULMINATION OF DECADES OF R & D, DESIGNED POC SIMPLE OPERATION, LOW COST AND LARGE-SCALE PRODUCTION. LEVERAGING ON THE BGM TECHNOLOGY, WE CAN SIGNIFICANTLY REDUCE THE TIME AND COST ASSOCIATED WITH DEVICE DEVELOPMENT AND SCALE-UP PRODUCTION. IN THIS PROPOSED PHASE I PROJECT, WE WILL DEMONSTRATE THE FEASIBILITY OF A POC SCREENING TEST FOR ORAL CANCER BY DEVELOPING BGM BASED POC TESTS FOR IL-6 AND IL-8 AND VALIDATE THEIR PERFORMANCE IN RELEVANT SPECIMEN.