U01CA279866

Point-of-care diagnosis of esophageal cancer in LMICs - Summary: Despite substantial progress in clinical approaches to squamous cancer of the esophagus (ESCC), which causes most esophageal cancers (EC) in the world, this deadly tumor usually occurs at late disease stages, with very poor survival.

Restricted availability of endoscopy (EGD), along with rarity and delays in histology, impairs detection of ESCC in LMICs, adversely impacting our ability to treat this disease effectively. Thus, in LMICs, inexpensive, safe, locally performable strategies for detecting ESCC are necessary to identify high-risk patients and refer them quickly to suitable diagnostic and therapeutic options.

Therefore, a diagnostic approach featuring a retrievable swallowed sponge-on-a-string to gather esophageal specimens for molecular testing, combined with a point-of-care (POC) magnetofluidic chip for sample processing and DNA methylation detection, is proposed. The string-sponge is less expensive, more noninvasive, more convenient, and more rapid than EGD with biopsy. The magnetofluidic chip streamlines DNA purification, DNA bisulphite treatment, and PCR detection of methylation markers into a single POC apparatus.

This approach does not necessitate EGD, can be performed in remote areas with portable energy supplies and does not require extensive medical training, and is thereby amenable to implementation in LMICs. Our specific aims are:

1: Using a sponge-capsule swallowed/tethered collection device, to construct a methylation marker-based strategy to detect ESCC. In 100 ESCC and 100 benign control patients, we propose (1) building a multivariate model containing biomarker candidates; (2) carrying out feedback-feasibility meetings with health care and endoscopy personnel at Makerere University Hospitals to fine-tune eventual POC usage;

2: In order to achieve a sample-to-answer assay, to implement DNA extraction, bisulfite treatment, and methylation-specific PCR into a magnetofluidic chip with dried reagents. We'll use magnetofluidic techniques to streamline cell lysis, DNA extraction, bisulphite treatment, and methylation-specific PCR into a compact chip built from cheap thermoplastic materials. In addition, we'll lyophilize reagents and use heat-deployed wax sealant plugs to permit storage at room temperature. In this fashion, we will fashion a sample-to-answer assay that is easy to use, inexpensive, and free of cold-chain steps;

3: In order to achieve fully automatic high-speed biomarker assaying, to design a small, light apparatus. We'll engineer an instrument containing programmable magnetic actuation, temperature control, and detection of fluorescence to execute the test in a chip with very little user input. We'll also design the apparatus to be small, light, easy to operate, portable electricity-powered, and mobile phone-controlled to ease integration with LMIC-based clinical tasking; and

4: Using our POC approach to carry out a diagnostic pilot study of ESCC in Uganda. While applying the magnetofluidic chip and apparatus used in Aim 2 and Aim 3, we'll carry out a trial to measure specificity and sensitivity in 120 EGD-confirmed cases of ESCC and 360 benign disease control patients in Kampala, Uganda.

The Johns Hopkins University

TO IMPROVE SCREENING AND EARLY DETECTION STRATEGIES AND TO DEVELOP ACCURATE DIAGNOSTIC TECHNIQUES AND METHODS FOR PREDICTING THE COURSE OF DISEASE IN CANCER PATIENTS. SCREENING AND EARLY DETECTION RESEARCH INCLUDES DEVELOPMENT OF STRATEGIES TO DECREASE CANCER MORTALITY BY FINDING TUMORS EARLY WHEN THEY ARE MORE AMENABLE TO TREATMENT. DIAGNOSIS RESEARCH FOCUSES ON METHODS TO DETERMINE THE PRESENCE OF A SPECIFIC TYPE OF CANCER, TO PREDICT ITS COURSE AND RESPONSE TO THERAPY, BOTH A PARTICULAR THERAPY OR A CLASS OF AGENTS, AND TO MONITOR THE EFFECT OF THE THERAPY AND THE APPEARANCE OF DISEASE RECURRENCE. THESE METHODS INCLUDE DIAGNOSTIC IMAGING AND DIRECT ANALYSES OF SPECIMENS FROM TUMOR OR OTHER TISSUES. SUPPORT IS ALSO PROVIDED FOR ESTABLISHING AND MAINTAINING RESOURCES OF HUMAN TISSUE TO FACILITATE RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.394 - Cancer Detection and Diagnosis Research

National Cancer Institute (NCI) [HHS - NIH]

Baltimore, Maryland 212051832 United States

Single Zip Code

Cancer Prevention, Detection, Diagnosis, and Treatment Technologies for Global Health (U01 Clinical Trial Optional) (RFA-CA-22-020)

Amendment Since initial award the total obligations have increased 191% from $620,532 to $1,803,699.