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Targeting circRNA translation in glioblastoma

Award Number: R01CA278783
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2024
PERIOD OF PERFORMANCE END DATE: 02/28/2029

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Targeting circRNA translation in glioblastoma - Project Summary Glioblastomas are highly malignant and invasive, making these neoplasms extremely difficult to surgically resect and these properties often result in tumors which are refractory to standard chemotherapeutic therapies. Unfortunately monotherapies targeting known drivers of glioblastomas such as hyperactive EGFR and c-MET RTKs have proven to be ineffective suggesting redundant mechanisms of activation. We have identified circular RNA-derived proteins which are overexpressed in glioblastoma and these novel products are capable of stimulating receptor tyrosine kinase activity leading to enhanced proliferation, mobility and invasive characteristics. In this application we propose to 1.) determine the mechanism(s) of circ-HGF mediated activation of c-MET in glioblastoma, 2.) clarify the role of PKA/PTBP1 signaling in the regulation of circ-HGF and circ-E-Cad translation initiation and expression in GBM, 3.) evaluate a novel small molecule inhibitor of circ-HGF and circ-E-Cad IRES-dependent translation in orthotopic GBM PDX models. We also propose to investigate and chemically modify the inhibitor to build in desired anti-glioblastoma effects.


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 = $313,616 )
2025	2025	GREATER LOS ANGELES VETERANS RESEARCH AND EDUCATION FOUNDATION	11301 WILSHIRE BLVD BLDG 114 RM 218	LOS ANGELES	CA	90073	LOS ANGELES	USA	Cancer Treatment Research	000	2	2/12/2025	NON-COMPETING CONTINUATION	$282,255
2025	2025	GREATER LOS ANGELES VETERANS RESEARCH AND EDUCATION FOUNDATION	11301 WILSHIRE BLVD BLDG 114 RM 218	LOS ANGELES	CA	90073	LOS ANGELES	USA	Cancer Treatment Research	001	2	5/22/2025	NON-COMPETING CONTINUATION	$31,361
														Subtotal = $313,616

Issue Date FY: 2024 ( Subtotal = $313,616 )
2024	2024	GREATER LOS ANGELES VETERANS RESEARCH & EDUCATION FOUNDATION	11301 WILSHIRE BLVD BLDG 114 RM 218	LOS ANGELES	CA	90073	LOS ANGELES	USA	Cancer Treatment Research	000	1	2/26/2024	NEW	$313,616
														Subtotal = $313,616

Grand Total All Awards = $627,232

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Targeting circRNA translation in glioblastoma

Award Number: R01CA278783

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2024

PERIOD OF PERFORMANCE END DATE: 02/28/2029

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