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Stromal depletion for pancreatic cancer therapy

Award Number: R21CA176339
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2013
PERIOD OF PERFORMANCE END DATE: 09/30/2016

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Stromal depletion for pancreatic cancer therapy - DESCRIPTION (provided by applicant): This project is focused on developing an innovative treatment modality for pancreatic cancer, which is one of the most lethal human malignancies. This treatment modality consists of two components: an innovative drug with enhanced efficacy, and imaging techniques that can non-invasively monitor treatment responses to assist physicians adjusting the therapeutic plan accordingly. We will evaluate the efficacy of the agent and the sensitivity of the imaging methods in multiple primary tumor models in mice. It has been recognized that a pancreatic tumor contains not only malignant cells but also supporting cells and connective tissues, which are referred to as stroma collectively. Stroma is known to promote cancer progression and spread, and has been identified as a therapeutic target to enhance pancreatic cancer therapy. Unfortunately, the progress of developing a stroma-targeted drug has been limited, and almost all of the testing drugs have failed in early human trials. The recent encouraging data with Abraxane (a taxane drug with an improved formulation) in human patients suggest that taxanes can be an effective stromal depleting agent to enhance pancreatic cancer treatment if the drug delivery efficiency is improved. We have thus created an innovative formulation for docetaxel (named Cellax), which selectively accumulate in tumors for sustained drug release and prolonged efficacy. In a mouse pancreatic tumor model, Cellax depleted most of the stroma and eventually eliminated the pancreatic tumors. We plan to further evaluate Cellax in 5 human primary tumor models that better represent the human disease, and also to investigate if the existing MRI techniques can monitor therapeutic response after Cellax therapy. 1. Evaluate Cellax in 5 primary models of pancreatic cancer. We will compare the efficacy of Cellax for inhibiting stroma and tumor growth compared to native docetaxel and Abraxane. The toxicity of these drugs will also be compared. We will also compare these treatments for their intratumoral drug delivery and effects on tumor cells and stromal cells separately to determine their mode-of-action and whether Cellax exhibits improved antitumor efficacy via enhanced anti-stromal activity. 2. Investigate if MRI techniques can monitor therapeutic response of Cellax. We will investigate if existing MRI techniques (magnetization transfer MRI and dynamic contrast enhanced MRI) can sensitively monitor tumor stromal depletion and tumor vascularity changes after Cellax therapy in 2 selected primary models of pancreatic cancer. If successful, these immediately translatable MR techniques will enable clinical monitoring of the response of stromal depletion therapy and timely adjustment of the treatment plan. The overall goal is to create an enhanced treatment modality to improve pancreatic cancer care.


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: 2017 ( Subtotal = $0 )
2017	2014	UNIVERSITY OF BRITISH COLUMBIA, THE	6190 AGRONOMY RD STE 102	VANCOUVER	BC	V6T 1Z3		CAN	Cancer Treatment Research	000	3	2/1/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $0 )
2016	2014	UNIVERSITY OF BRITISH COLUMBIA	**	VANCOUVER, B C		00000		CAN	Cancer Treatment Research	000	3	6/13/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = $244,813 )
2014	2014	UNIVERSITY OF BRITISH COLUMBIA	2329 West Mall	VANCOUVER, B C				CAN	Cancer Treatment Research	001	3	9/15/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$123,139
2014	2014	ONTARIO INSTITUTE FOR CANCER RESEARCH	101 COLLEGE STREET	TORONTO				CAN	Cancer Treatment Research	000	2	6/23/2014	NON-COMPETING CONTINUATION	$121,674
2014	2014	ONTARIO INSTITUTE FOR CANCER RESEARCH	101 COLLEGE STREET	TORONTO				CAN	Cancer Treatment Research	002	2	9/15/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $244,813

Issue Date FY: 2013 ( Subtotal = $129,195 )
2013	2013	ONTARIO INSTITUTE FOR CANCER RESEARCH	101 COLLEGE ST, STE 800	TORONTO				CAN	Cancer Treatment Research	000	1	7/1/2013	NEW	$129,195
														Subtotal = $129,195

Grand Total All Awards = $374,008

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Stromal depletion for pancreatic cancer therapy

Award Number: R21CA176339

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2013

PERIOD OF PERFORMANCE END DATE: 09/30/2016

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