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Targeting vulnerabilities of therapy-resistant cancer cell states with small molecules

Award Number: U01CA217848
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2017
PERIOD OF PERFORMANCE END DATE: 07/31/2022

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Targeting vulnerabilities of therapy-resistant cancer cell states with small molecules - ABSTRACT Targeted therapies and immunotherapies are two of the most transformative and promising advances in cancer treatment over the last two decades. Yet they, like conventional chemotherapies, frequently succumb to the ability of cancers eventually to resist therapeutic attacks on their vulnerabilities, reversing the initially impressive clinical responses to these treatments. This project focuses on conserved non-mutational mechanisms of resistance that are frequently encountered in resistance arising in multiple therapeutic regimens across multiple cancer types. In the current phase of the CTD2 Network, we developed powerful new tools and capabilities that enable the community to identify novel cancer vulnerabilities. The method relies on the Cancer Therapeutics Response Portal (CTRP), which houses a large dataset of quantitative compound sensitivity data and has been made available without restriction. Using CTRP, we found evidence for the existence of at least one such common therapy-resistant state, associated with mesenchymal characteristics of cancer cells. Importantly, this state emerges from treatment with either chemotherapy or targeted therapeutics across several cancer types. This project aims to fully dissect this pathway, and to discover other such pathways, to understand the bases of resistant-state vulnerabilities, and to learn how to exploit them therapeutically in a safe and effective way.


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: 2023 ( Subtotal = -$839 )
2023	2021	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	000	5	4/11/2023	NON-COMPETING CONTINUATION	-$839
														Subtotal = -$839

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	000	5	3/21/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $1,196,073 )
2021	2021	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	001	5	8/4/2021	NON-COMPETING CONTINUATION	$1,021,073
2021	2021	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	002	5	9/21/2021	NON-COMPETING CONTINUATION	$175,000
2021	2020	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	000	4	5/14/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,196,073

Issue Date FY: 2020 ( Subtotal = $1,196,074 )
2020	2020	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	001	4	7/31/2020	NON-COMPETING CONTINUATION	$1,196,074
2020	2019	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	000	3	1/30/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,196,074

Issue Date FY: 2019 ( Subtotal = $1,140,443 )
2019	2019	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	002	3	9/4/2019	NON-COMPETING CONTINUATION	$150,000
2019	2019	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	001	3	8/1/2019	NON-COMPETING CONTINUATION	$990,443
2019	2018	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	000	2	3/18/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,140,443

Issue Date FY: 2018 ( Subtotal = $1,146,076 )
2018	2018	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	000	2	7/10/2018	NON-COMPETING CONTINUATION	$1,021,075
2018	2018	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	001	2	9/11/2018	NON-COMPETING CONTINUATION	$125,001
														Subtotal = $1,146,076

Issue Date FY: 2017 ( Subtotal = $1,146,075 )
2017	2017	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	003	1	9/22/2017	NEW	$0
2017	2017	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	002	1	8/25/2017	NEW	$125,000
2017	2017	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	001	1	8/23/2017	NEW	$154,404
2017	2017	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	000	1	8/1/2017	NEW	$866,671
														Subtotal = $1,146,075

Grand Total All Awards = $5,823,902

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Targeting vulnerabilities of therapy-resistant cancer cell states with small molecules

Award Number: U01CA217848

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 08/01/2017

PERIOD OF PERFORMANCE END DATE: 07/31/2022

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