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Addressing biological and therapeutic gaps in rare neuroendocrine cancer with a novel organoid-based model

Award Number: R01CA264248
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/08/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Addressing biological and therapeutic gaps in rare neuroendocrine cancer with a novel organoid-based model - This proposal responds to the provocative question PQ9: What methods can be developed to effectively study small or rare populations relevant to cancer research? We will address this question by generating organoid models of pheochromocytomas and paragangliomas (PPGL) to fill gaps in the mechanisms underlying tumor behavior and in therapeutic opportunities. PPGLs are rare catecholamine-secreting, neural crest-derived tumors originating from adrenal or extra adrenal paraganglia, respectively. Malignant PPGLs can only be recognized after detection of metastases, implying a late diagnosis. Approximately 30-40% of paragangliomas, and 10-15% of pheochromocytomas can develop metastases. In addition, PPGLs are clinically heterogeneous, can be recurrent and invasive, even without metastasis, but predictors of clinical behavior are lacking. Treatment options are currently limited, with modest effects on survival, and advances in this area are dampened by a scarcity of research models. Therefore, there is a critical need for developing models to uncover biological mechanisms that facilitate clinical outcome prediction and reveal molecular vulnerabilities which can be explored for therapeutic purposes. Our preliminary data indicate that we can successfully generate PPGL organoids that are amenable for drug screen. Our aims are: 1) to determine if PPGL organoids recapitulate features of the parental tumor; 2) to leverage PPGL organoids to investigate outstanding biological questions, including the existence of cell subtypes that may be related to tumor outcome, and 3) to utilize PPGL organoids for high- throughput drug screening that uncover vulnerabilities for future therapeutic testing, including novel leads suggested in our preliminary data. The proposed project will serve as a useful resource for designing future studies to decode the cellular and molecular mechanisms underlying PPGL development and clinical heterogeneity. Results from these studies may provide the groundwork for future testing of candidate drugs that might have immediate clinical application.


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: 2025 ( Subtotal = $808,500 )
2025	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Biology Research	001	5	9/4/2025	SUPPLEMENT FOR EXPANSION	$74,115
2025	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Biology Research	002	5	9/8/2025	SUPPLEMENT FOR EXPANSION	$237,198
2025	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Biology Research	003	5	9/12/2025	NON-COMPETING CONTINUATION	-$311,313
2025	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Biology Research	000	5	9/3/2025	NON-COMPETING CONTINUATION	$808,500
														Subtotal = $808,500

Issue Date FY: 2024 ( Subtotal = $805,017 )
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Biology Research	002	4	8/7/2024	SUPPLEMENT FOR EXPANSION	$237,196
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Biology Research	001	4	8/6/2024	SUPPLEMENT FOR EXPANSION	$70,409
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Biology Research	000	4	8/2/2024	NON-COMPETING CONTINUATION	$468,662
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Biology Research	003	4	8/29/2024	SUPPLEMENT FOR EXPANSION	$28,750
														Subtotal = $805,017

Issue Date FY: 2023 ( Subtotal = $557,576 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Biology Research	001	3	9/18/2023	SUPPLEMENT FOR EXPANSION	$74,115
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Biology Research	000	3	7/27/2023	NON-COMPETING CONTINUATION	$483,461
														Subtotal = $557,576

Issue Date FY: 2022 ( Subtotal = $483,461 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Biology Research	000	2	8/31/2022	NON-COMPETING CONTINUATION	$483,461
														Subtotal = $483,461

Issue Date FY: 2021 ( Subtotal = $525,382 )
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Cancer Biology Research	000	1	9/8/2021	NEW	$525,382
														Subtotal = $525,382

Grand Total All Awards = $3,179,936

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Addressing biological and therapeutic gaps in rare neuroendocrine cancer with a novel organoid-based model

Award Number: R01CA264248

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/08/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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