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Mechanistic insights into cisplatin resistance during secondhand smoke exposure

Award Number: R03DE036378
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: 09/16/2026
PERIOD OF PERFORMANCE END DATE: 09/15/2028

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Mechanistic insights into cisplatin resistance during secondhand smoke exposure - Project Summary Side stream (SS) smoke, released from cigarette tips, comprises 85% of secondhand smoke (SHS). SS smoke is significantly different from active cigarette smoke and contains higher levels of several carcinogens (eg. TSNA, AA, and certain PAHs) that are linked to drug resistance. U.S. government policies and other regulatory actions have reduced SHS exposure levels from 52.5% to 25.3% in the last 20 years; yet 1 in 5 Americans and 16% of non-smoking cancer survivors are involuntarily exposed to SHS. States with partial smoke-free laws further increase these exposure levels. SHS exposure is associated with increased cancer recurrence and decreased disease-free survival in patients with head and neck squamous cell carcinoma (HNSCC). Our data confirmed that human-relevant SS smoke exposure significantly increased cisplatin resistance through reduced cisplatin-induced cell death, and increased cell viability & colony formation in diverse HNSCC cells. Further, proteomic analysis revealed several genes/pathways that are crucial for cell survival were altered in HNSCC after exposure to SS smoke. However, the mechanistic insights of these altered pathways associated with cisplatin resistance in HNSCC in the context of SS smoke exposure is unknown. To fill the knowledge gap, the proposed study will determine the mechanism by which SS smoke mediates cisplatin-resistance in HNSCC through two specific aims: (1) Determine the mechanism by which SS smoke induces HNSCC cisplatin- resistance using a patient-derived organoid in vitro model, and (2) Evaluate the SHS exposure-induced cisplatin resistance in the HNSCC patient-derived xenograft mouse model. Findings from this proposed study will not only advance our knowledge on the understanding of SHS exposure-associated cisplatin resistance, will also identify a biomarker to overcome this observed cisplatin resistance, which is crucial to achieve HNSCC patients' maximum treatment benefits.


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 = $286,000 )
2026	2026	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 560	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Oral Diseases and Disorders Research	000	1	9/17/2026	NEW	$286,000
														Subtotal = $286,000

Grand Total All Awards = $286,000

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Mechanistic insights into cisplatin resistance during secondhand smoke exposure

Award Number: R03DE036378

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: 09/16/2026

PERIOD OF PERFORMANCE END DATE: 09/15/2028

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