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Smooth muscle invasion selects for aggressive prostate cancer

Award Number: F30CA247106
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Smooth muscle invasion selects for aggressive prostate cancer - PROJECT SUMMARY/ABSTRACT The most common non-cutaneous cancer in American men, prostate cancer is characterized by a substantial degree of overdiagnosis and is consequently a significant source of morbidity and driver of unnecessary cost. There is therefore a significant need to identify prostate cancer patients who need aggressive therapy compared to those who need no treatment at all. The cancer-specific mortality of these tumors is attributable to metastatic disease. Adenocarcinoma of the prostate must interact with smooth muscle at multiple steps of the metastatic process, including intravasation and extravasation between the bloodstream and tissue. In addition, the cancer- prone peripheral zone of the human prostate gland is composed of a fibromuscular stroma and bounded by a smooth muscle capsule. While the current paradigm for most cancers is that local invasion is not predictive of aggressive disease, this is not the case with prostate cancer. Aggressive prostate cancer cells are directly observed as extending past the smooth muscle capsule in clusters, in a process called extracapsular extension (ECE), thereby escaping organ confinement. The presence of ECE defines the pT3a category in the pathologic staging of prostatic adenocarcinoma and is associated with an increased risk of biochemical recurrence, distant metastases and cancer-specific mortality. Although smooth muscle invasion is required for ECE, intravasation, and extravasation to distant sites, there are no markers of the switch from indolent to aggressive, muscle-invasive prostate cancer. This work is therefore concentrated on understanding the molecular events that regulate ECE to prevent this critical step in the metastatic process. The central hypothesis is that invasion through the smooth muscle capsule requires unique molecular properties that predict aggressive cancer. If correct, the concept will change current standard of care by providing new molecular discriminators of indolent versus aggressive disease. Objective measures of the aggressive disease transition will inform treatment decisions and help to direct the appropriate level of treatment for the degree of disease aggression.


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 = -$2,348 )
2025	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Research Manpower	000	4	4/24/2025	NON-COMPETING CONTINUATION	-$2,348
														Subtotal = -$2,348

Issue Date FY: 2023 ( Subtotal = $52,055 )
2023	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Research Manpower	000	4	6/26/2023	NON-COMPETING CONTINUATION	$52,055
														Subtotal = $52,055

Issue Date FY: 2022 ( Subtotal = $51,113 )
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Research Manpower	000	3	6/10/2022	NON-COMPETING CONTINUATION	$51,113
														Subtotal = $51,113

Issue Date FY: 2021 ( Subtotal = $37,999 )
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Research Manpower	000	2	5/14/2021	NON-COMPETING CONTINUATION	$37,999
														Subtotal = $37,999

Issue Date FY: 2020 ( Subtotal = $37,483 )
2020	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Research Manpower	000	1	6/25/2020	NEW	$37,483
2020	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Research Manpower	001	1	6/25/2020	NEW	$0
														Subtotal = $37,483

Grand Total All Awards = $176,302

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Smooth muscle invasion selects for aggressive prostate cancer

Award Number: F30CA247106

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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