Monday, June 30, 2025 6/30/2025

CAPER, a New Regulator of DNA Damage and Repair in Triple Negative Breast Cancer

Award Number: R15CA242344
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/21/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2025

Group Awards By:

View Award Description

CAPER, a New Regulator of DNA Damage and Repair in Triple Negative Breast Cancer - ABSTRACT Triple negative breast cancer (TNBC) has the poorest clinical outcome amongst all breast cancer subtypes. TNBC lacks the expression of the three major receptors found in other subtypes (estrogen receptor [ER], progesterone receptor, and/or hormone epidermal growth factor receptor-2) making this cancer particularly challenging with regards to treatment modalities. Novel targeted treatments that could kill TNBC cells or sensitize them to chemo- and radiation therapies are highly coveted to increase survival of these patients. Due to its fast proliferative rate, TNBC relies heavily on DNA repair mechanisms for its survival and proteins involved in this important checkpoint are attractive targets for cancer treatment. CAPER (Rbm39) protein was recently shown to be overexpressed in breast cancer specimens compared to normal breast tissues. While CAPER knockdown inhibits breast cancer cell growth, its role on DNA damage and repair mechanisms in breast cancer and its role in TNBC progression and response to chemo- and radiation therapies remain completely unexplored. Our preliminary data demonstrate that knockdown of CAPER expression in TNBC cells increases DNA damage as reflected by increased phosphorylation of H2AX and ATM. The decreased total cell number and increased caspase-3/7 cleavage observed following CAPER knockdown in MDA-MB-231 and BT549 TNBC cells is suggestive of insurmountable DNA damage leading to programmed cell death (apoptosis). The effect of CAPER knockdown on DNA damage in TNBC cells was cell cycle-independent and selective to cancer cells, as non- tumorigenic cells lack the expression of CAPER and remain unaffected following delivery of lentiviral CAPER shRNAs. Our preliminary results also revealed that DNA repair proteins RAD-51, C-Alb and RB were significantly downregulated in TNBC following CAPER knockdown. We posit that CAPER overexpression in TNBC plays an important role in protection against DNA damage by optimizing DNA repair pathways. The current proposal builds on our previous work and preliminary results and aims to delineate the roles of CAPER in basal DNA damage/repair pathways and to determine its clinical relevance in TNBC growth using both immunocompromised (xenograft) and immunocompetent (syngeneic) orthotopic mouse models (Aim 1). Importantly, we will also use these TNBC cells and mouse models to test the unexplored role of CAPER in the response to DNA damaging chemo- and radiation therapies in both in vitro and in vivo settings (Aim 2). The current proposal will validate the role of CAPER as an important signaling molecule in the progression of TNBC as well as response to DNA damage using clinically relevant models that also incorporate immune surveillance and will be insightful in the further development of targeted therapies for the treatment of TNBC.


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: 2022 ( Subtotal = $434,998 )
2022	2022	ST JOSEPH'S UNIVERSITY	5600 CITY AVE	PHILADELPHIA	PA	19131	PHILADELPHIA	USA	Cancer Cause and Prevention Research	000	1	9/21/2022	NEW	$434,998
														Subtotal = $434,998

Grand Total All Awards = $434,998

Top

All Categories

About

Search

Reports

Data Submission

Award Information

CAPER, a New Regulator of DNA Damage and Repair in Triple Negative Breast Cancer

Award Number: R15CA242344

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/21/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer