Tuesday, November 4, 2025 11/4/2025

Protein-DNA Drug Carriers for Targeting Drug-Resistant Tumors

Award Number: R01CA129822
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2007
PERIOD OF PERFORMANCE END DATE: 07/31/2021

Group Awards By:

View Award Description

Protein-DNA Drug Carriers for Targeting Drug-Resistant Tumors - DESCRIPTION (provided by applicant): Elevated cell surface levels of the human epidermal growth factor receptor subunit 3 (HER3) is associated with resistance to a number of signal-blocking breast cancer treatments, including inhibitors of EGF-R (lapatinib), HER2 (lapatinib, trastuzumab, T-DM1), HER2-3 (pertuzumab), and combination therapy. Additionally, HER3 elevation has been identified on "untarget-able" tumors such as triple-negative breast cancer (TNBC), including TNBC with acquired resistance to EGF-R inhibition. Patients with such refractory tumors currently have limited treatment options and a poor prognosis. Moreover, as up to 70% of cases resist or acquire resistance to signal-blocking therapies, an alternative approach addressing this important clinical problem has the potential for significant clinical impact. We have developed a self-assembling nanobiological particle, HerDox, which uses HER3 as a portal for targeted entry of toxic molecules. In contrast to receptor-targeted antibodies and tyrosine kinase inhibitors currently used in the clinic, HerDox circumvents the need to modulate signaling and can induce rapid entry of toxic molecules into tumor cells by receptor-mediated endocytosis and membrane penetration. We have previously shown that HerDox can elicit targeted toxicity to HER2+ tumors due to the prevalence of HER2-3 heterodimers on the tumor cell surface, while sparing heart and liver tissue. We are currently exploring the capacity for HerDox to target toxicity to tumors that resist HER2 inhibitors. Our preliminary studies show that HerDox exhibits improved therapeutic efficacy on tumor cell lines with acquired resistance to HER2 inhibitors over parental tumor cells, due in part to the elevated HER3 expression associated with the HER2+ drug resistance. Here we will evaluate the mechanism and efficacy of HerDox in several in vitro and in vivo models representing distinct scenarios along the spectrum of resistance. We will probe the additional factors contributing to the high efficacy of HerDox on tumors with acquired resistance, as these cells exhibit moderately elevated levels of HER3. We will evaluate the efficacy of using signal-inhibitors as adjuvants for HerDox treatment on both naïve and inherently-resistant tumors, given the preliminary finding that pretreatment of parental breast cancer cell lines in vitro with trastuzuma induced elevation of HER3. We will also evaluate the efficacy of HerDox on TNBC in an immunocompetent model of disseminated breast cancer and assess whether EGF-R inhibition further sensitizes these tumors to HerDox via HER3 elevation. In all aims of this study, HerDox will be evaluated in comparison to trastuzumab, lapatinib, pertuzumab, T-DM1, and combination treatments. The advantages over signal-blocking inhibitors seen in our preliminary studies suggest that HerDox is likely to present an effective approach in addressing tumors that resist current targeted treatments used in the clinic.


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 = -$71,251 )
2022	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Treatment Research	000	10	11/24/2021	NON-COMPETING CONTINUATION	-$71,251
														Subtotal = -$71,251

Issue Date FY: 2020 ( Subtotal = $261,782 )
2020	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Treatment Research	000	10	7/24/2020	NON-COMPETING CONTINUATION	$261,782
														Subtotal = $261,782

Issue Date FY: 2019 ( Subtotal = $101,059 )
2019	2019	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Treatment Research	000	9	9/16/2019	NON-COMPETING CONTINUATION	$101,059
														Subtotal = $101,059

Issue Date FY: 2018 ( Subtotal = $374,063 )
2018	2018	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Treatment Research	000	8	8/14/2018	NON-COMPETING CONTINUATION	$374,063
														Subtotal = $374,063

Issue Date FY: 2017 ( Subtotal = $374,063 )
2017	2017	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Treatment Research	000	7	7/24/2017	NON-COMPETING CONTINUATION	$374,063
														Subtotal = $374,063

Issue Date FY: 2016 ( Subtotal = $374,063 )
2016	2016	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Treatment Research	000	6	8/2/2016	NON-COMPETING CONTINUATION	$374,063
														Subtotal = $374,063

Issue Date FY: 2015 ( Subtotal = $374,063 )
2015	2015	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Treatment Research	000	5	7/24/2015	COMPETING CONTINUATION	$374,063
														Subtotal = $374,063

Issue Date FY: 2012 ( Subtotal = $288,593 )
2012	2012	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Treatment Research	000	4	4/5/2012	NON-COMPETING CONTINUATION	$288,593
														Subtotal = $288,593

Issue Date FY: 2011 ( Subtotal = $294,365 )
2011	2011	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Treatment Research	000	3	4/7/2011	EXTENSION WITH OR WITHOUT FUNDS	$273,122
2011	2011	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Treatment Research	002	3	5/16/2011	EXTENSION WITH OR WITHOUT FUNDS	$21,243
2011	2010	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Trans-NIH Recovery Act Research Support	001	2	4/7/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $294,365

Issue Date FY: 2010 ( Subtotal = $303,469 )
2010	2010	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Trans-NIH Recovery Act Research Support	000	2	4/30/2010	NON-COMPETING CONTINUATION	$303,469
														Subtotal = $303,469

Issue Date FY: 2009 ( Subtotal = $272,345 )
2009	2009	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Trans-NIH Recovery Act Research Support	000	1	4/27/2009	NEW	$272,345
														Subtotal = $272,345

Grand Total All Awards = $2,946,614

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Protein-DNA Drug Carriers for Targeting Drug-Resistant Tumors

Award Number: R01CA129822

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2007

PERIOD OF PERFORMANCE END DATE: 07/31/2021

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer