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Role of CASP8 and HRAS co-mutation in oral epithelium malignant transformation

Award Number: R03DE035544
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Role of CASP8 and HRAS co-mutation in oral epithelium malignant transformation - PROJECT SUMMARY/ABSTRACT Smoking-associated, HPV-negative oral squamous cell carcinoma (OSCC) is highly aggressive, with a five-year survival rate below 50% for advanced-stage patients. HRAS and CASP8 mutations frequently co-occur in OSCC, yet their functional roles in tumor development remain unstudied. This research aims to investigate the impact of HRAS/CASP8 co-mutations on oral epithelial malignant transformation using a tamoxifen-inducible, oral epithelium-specific knock-in mouse model. Through high-throughput Imaging Mass Cytometry, the study will characterize tumor-intrinsic proliferation, cell death resistance, and immune evasion mechanisms associated with these mutations. Specifically, Aim 1 will determine whether HRAS and CASP8 co-mutations are sufficient to drive spontaneous oral carcinogenesis and define the underlying mechanisms, whereas Aim 2 will test whether CASP8/HRAS co-mutations can serve as predictive markers for high-risk premalignant oral lesions by defining their emergence stage using amplicon NGS in a longitudinal cohort of patients with high- and low-risk lesions. Overall, this study aims to identify predictive biomarkers for early cancer detection and risk assessment, informing precision medicine approaches and guiding surgical and therapeutic strategies to improve patient outcomes.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $320,200 )
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Oral Diseases and Disorders Research	000	1	8/27/2026	NEW	$320,200
														Subtotal = $320,200

Grand Total All Awards = $320,200

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Role of CASP8 and HRAS co-mutation in oral epithelium malignant transformation

Award Number: R03DE035544

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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