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Normalizing PDAC stroma with PCBP2 siRNA nanoparticles to improve the antitumor activity of chemotherapy and immunotherapy

Award Number: R01CA271592
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Normalizing PDAC stroma with PCBP2 siRNA nanoparticles to improve the antitumor activity of chemotherapy and immunotherapy - Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality in the world. Desmoplasia is the most prominent characteristic of PDAC and comprises up to 80% of the tumor mass. Desmoplasia plays important roles in tumorigenesis and aggressiveness by promoting the proliferation and metastasis of tumor cells, enhancing angiogenesis, impeding drug penetration, and contributing to immune evasion. However, clinical trials employing strategies to deplete PDAC stroma have failed. The stroma acts not only as a barrier to the penetration of drug and effector T cells, but also as a barrier to restrain the metastasis of PDAC tumors. Complete depletion of the stroma, therefore, leads to a more aggressive tumor and a poor survival rate. By contrast, normalization, instead of depletion, of the stroma in combination with chemotherapy or immunotherapy to kill tumor cells within the stromal microenvironment is a promising strategy for PDAC therapy. In the stromal microenvironment, activated pancreatic stellate cells (PSCs) transform from a quiescent state into a myofibroblast-like phenotype and express a large amount of extracellular matrix (ECM). Type I collagen proteins are the main component of the ECM and are responsible for the major desmoplastic reaction. High levels of type I collagen are associated with a low survival rate for patients with PDAC. Type I collagen promotes the proliferation and migration of PDAC cells and inhibits apoptotic cells by binding to integrin. We discovered that silencing the poly(rC)-binding protein 2 (αCP2) with siRNA reverses the accumulation of type I collagen in activated PSCs. Our central hypothesis is that silencing αCP2 modulates the PDAC stroma, thus improving the therapeutic index of chemotherapy and immunotherapy. The long-term goal of the project is to develop a combination therapy strategy to treat PDAC.


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 = $330,814 )
2025	2025	THE CURATORS OF THE UNIVERSITY OF MISSOURI	118 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cancer Treatment Research	000	3	3/4/2025	NON-COMPETING CONTINUATION	$330,814
														Subtotal = $330,814

Issue Date FY: 2024 ( Subtotal = $349,193 )
2024	2024	THE CURATORS OF THE UNIVERSITY OF MISSOURI	118 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cancer Treatment Research	000	2	3/28/2024	NON-COMPETING CONTINUATION	$330,814
2024	2024	THE CURATORS OF THE UNIVERSITY OF MISSOURI	118 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cancer Treatment Research	001	2	4/17/2024	NON-COMPETING CONTINUATION	$18,379
														Subtotal = $349,193

Issue Date FY: 2023 ( Subtotal = $368,579 )
2023	2023	UNIVERSITY OF MISSOURI SYSTEM	1011 E 51ST ST	KANSAS CITY	MO	64110	JACKSON	USA	Cancer Treatment Research	000	1	3/17/2023	NEW	$368,579
														Subtotal = $368,579

Grand Total All Awards = $1,048,586

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Normalizing PDAC stroma with PCBP2 siRNA nanoparticles to improve the antitumor activity of chemotherapy and immunotherapy

Award Number: R01CA271592

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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