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Principal Investigator: Sapun H Parekh
Organization: UNIVERSITY OF TEXAS AT AUSTIN
Fiscal Year: 2024
Award: $203,610
Funding agency: National Cancer Institute
ABSTRACT Melanoma is the fifth most common cancer in the US with almost 100,000 cases estimated for
2023. Late-stage disease has a five-year survival of just 30%, resulting in almost 8,000 deaths in the US alone.
When detected early, melanoma has a survival rate of 99%; however, a widely adopted screening tool for
melanoma currently does not exist. The current standard of care in skin cancer detection relies on a clinical
visual assessment of moles, followed by an invasive biopsy of suspicious lesions. The low accuracy of this
approach (84% sensitivity and 3-16% specificity) leads to missed melanomas and high rates of “unnecessary
biopsies”, biopsies of benign moles. An average of 25 biopsies are required for each melanoma found, resulting
in 3 million biopsies of benign moles each year. For this reason, the US Preventative Services Task Force does
not recommend routine visual screening for skin cancer in adults, citing the potential harm of the high rate of
unnecessary biopsies. Non-invasive genetic or spectroscopic tests that are currently available have either
sensitivities that are too low (below 98%) or specificities that are too low (below visual assessment). We
hypothesize that limited applicability of these approaches stems from the limited availability of melanoma
biomarkers. Studies have shown that a combination genetic markers and histological analysis offer an excellent
combination for specific and sensitive diagnosis; however, no minimally-invasive technology exists to provide
samples for this purpose. We propose a “laser microbiopsy” as a technique to harvest microliter-sized tissues,
using a ring-shaped infrared laser such that the center of the annulus can be removed with minimal damage by
a pulse of light. Because laser tissue removal is essentially instantaneous (within microseconds) and the biopsy
size is on the scale of hundreds of micrometers, the procedure is potentially much less harmful than traditional
punch biopsies. Importantly, our preliminary work shows that the laser microbiopsy penetrates through the
epidermis and to the melanocytes, where melanoma originates. To further develop this approach, we will refine
and characterize the performance of the laser microbiopsy hardware (Aim 1) and validate viability of extracted
micro-biopsies for molecular analysis (Aim 2). We envision our approach providing pain-free tissue for offline
pathology and molecular analysis of melanoma as well as a possible surgical guidance tool for real-time
assessment of tumor margins. In addition, harvested tissues could be used for primary tissue cultures or flow
cytometry. Once this proof-of-principle (R61) project is complete, we anticipate transitioning the laser
microbiopsy from a developmental phase to test feasibility for melanoma diagnosis in an R33 application.
Terms: <21+ years old><Abscission><Address><Adopted><Adult><Adult Human><Affect><Animals><Basal Layer><Benign><Biological Markers><Biopsy><Biopsy Sample><Biopsy Specimen><Body Tissues><Cancer Detection><Cancers><Cell Body><Cell Culture Techniques><Cells><Cessation of life><Clinic><Clinical><Collection><Computer Models><Computerized Models><Cone><Culturing, in vitro Vertebrate, Primary><Cytology><Data><Death><Dependence><Development><Device Designs><Devices><Diagnosis><Diameter><Disease><Disorder><Doppler OCT><Early Diagnosis><Ensure><Epidermis><Excision><Extirpation><Family suidae><Feasibility Studies><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Future><Genetic><Genetic Markers><Genetic analyses><Geometry><Harvest><Histologic><Histologically><Histology><Histopathology><Horny Layer><Human><Ice Cream><Illumination><Image><Immunofluorescence><Immunofluorescence Immunologic><Individual><Laser Electromagnetic><Laser Radiation><Lasers><Lesion><Light><Lighting><Malignant Melanoma><Malignant Neoplasms><Malignant Skin Neoplasm><Malignant Tumor><Mass Photometry/Spectrum Analysis><Mass Spectrometry><Mass Spectroscopy><Mass Spectrum><Mass Spectrum Analyses><Mass Spectrum Analysis><Mechanics><Melanoma><Methods><Microscope><Microscopy><Modeling><Modern Man><Mole the mammal><Molecular><Molecular Analysis><Moles><Morphology><Non-Polyadenylated RNA><OCT Tomography><Operative Procedures><Operative Surgical Procedures><Optical Coherence Tomography><Optics><Outcome><Pain><Pain Free><Painful><Pathologic><Pathology><Penetration><Performance><Phase><Photoradiation><Physiologic pulse><Pigs><Primary Cell Cultures><Procedures><Process><Property><Protein Analysis><Proteins><Pulse><Punch Biopsy><RNA><RNA Gene Products><Removal><Rete Malpighii><Ribonucleic Acid><Sampling><Screening for Skin Cancer><Screening procedure><Shapes><Skin><Skin Cancer><Slide><Specificity><Staining method><Stains><Stratum Basale><Stratum Germinativum><Stratum corneum><Suidae><Surface><Surgical><Surgical Interventions><Surgical Procedure><Surgical Removal><Survival Rate><Swine><Techniques><Technology><Testing><Time><Tissue Harvesting><Tissue Viability><Tissues><U.S. Preventative Services Task Force><U.S. Preventative Task Force><U.S. Preventive Services Task Force><U.S. Preventive Task Force><US Preventative Services Task Force><US Preventative Task Force><US Preventive Health Services Task Force><US Preventive Services Task Force><US Preventive Task Force><USPSTF><United States Preventative Services Task Force><United States Preventative Task Force><United States Preventive Services Task Force><United States Preventive Task Force><Visual><Work><adulthood><bio-markers><biologic marker><biomarker><biomarker of triple-negative melanoma><burden of disease><burden of illness><cell culture><cell cultures><computational modeling><computational models><computer based models><computerized modeling><conditioning><developmental><disease burden><dosimetry><early detection><experiment><experimental research><experimental study><experiments><feasibility testing><flow cytophotometry><gene biomarker><gene expression biomarker><gene marker><gene signature biomarker><genetic analysis><genetic approach><genetic biomarker><genetic strategy><imaging><improved><in silico><malignancy><malignant skin tumor><mechanic><mechanical><mechanical properties><melanocyte><melanoma associated biomarker><melanoma biomarkers><meter><microscope imaging><microscopic imaging><microscopy imaging><minimally invasive><molecular diagnostics><neoplasm/cancer><new technology><novel technologies><optic imaging><optical><optical Doppler tomography><optical coherence Doppler tomography><optical imaging><porcine><preconditioning><resection><screening><screening tools><screenings><skin cancer early detection><standard of care><stem><suid><surgery><tissue culture><tool><transcriptomics><tumor>