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SPORE in Skin Cancer

Award Number: P50CA174523
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/16/2014
PERIOD OF PERFORMANCE END DATE: 08/31/2021

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SPORE in Skin Cancer - DESCRIPTION (provided by applicant): The intent of the Penn/Wistar SPORE in Skin Cancer is to decrease the morbidity and mortality of skin cancers through the development of targeted therapies. This SPORE investigates three major skin cancers-melanoma, cutaneous T cell lymphoma (CTCL) and squamous cell carcinoma (SCC). The projects and cores focus on the leading cause of skin cancer deaths, melanoma. Our overarching hypothesis is that maximal long-lasting clinical impact achieved by interfering with signaling pathways and/or stimulating the host immune response requires that we take into account tumor-specific and host-specific genetic and epigenetic signatures. Each of the four projects has clear translational objectives and specific hypotheses that rest on a solid body of preliminary studies. The three cores support the projects and the developmental research and career developmental programs. The first overall objective is to develop novel therapies in melanoma. In three bf the four projects, we propose clinical trials of advanced metastatic melanoma with the overall hypothesis that melanoma is not a homogenous disease and, therefore, should be treated with different strategies. Projects 1 and 2 capitalize on our previous findings that two of the major druggable resistance mechanisms to BRAF inhibition in BRAF-mutant melanoma are activation of PI3K signaling and autophagy. Project 1 (Herlyn/Schuchter) proposes extensive tissue-based studies to understand the effects of concurrently targeting mutant BRAF and P13K. We expect the combination to be more effective in killing tumor cells and preventing or extending recurrence in a large subset of patients. Project 2 (Amaravadi/Speicher) combines autophagy and BRAF inhibition in patients with BRAF-mutant melanoma, and identifies other effective targeted therapy and autophagy inhibitor combination strategies that have future development potential for BRAF wild-type patients. Project 4 (Vonderheide/Kalos/June) deals with immunotherapy of melanoma by adoptive transfer of lymphocytes that are engineered to bind to tumor cells. The project is built on highly encouraging data from other malignancies that show activated T cells can achieve effective tumor regression and lasting clinical responses. The second overall objective is to establish new biomarkers in advanced melanoma. We hypothesize that identification of meaningful biomarkers not only will increase our knowledge of the dynamics of disease regression and progression before, during, and after therapy, but also will directly impact the management of the disease by tailored selection of therapy for patients, improved assessment during therapy, and enhanced outcome prediction. In projects 1 and 2, we will analyze patients' melanomas for genetic abnormalities with the intent of stratifying them prior to initiation of therapy into at least five different disease groups that will dictate therapeutic decision-making. We also will determine whether therapy-related changes can be detected in the sera (Project 2), tumors (Projects 1 and 2), and/or blood (Project 4) of patients. Finally, project 3 (Nathanson/Kanetsky) is a genome-wide association study that will investigate inherited genetic susceptibility to acute toxicities and outcomes of immunostimulatory therapy using the anti-CTLA4 drug, Ipilimumab. Here we expect to discover novel genetic signatures that may, after further study, facilitate identification of patient subgroups to help tailor therapeutic decision-making. We expect that this highly interactive SPORE program will yield tangible results for clinical practice in melanoma and other cancers of the skin.


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 = -$149,503 )
2022	2018	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	5	12/21/2021	NON-COMPETING CONTINUATION	-$149,503
														Subtotal = -$149,503

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	5	9/14/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	5	4/18/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $2,300,000 )
2018	2018	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	5	8/16/2018	NON-COMPETING CONTINUATION	$2,300,000
														Subtotal = $2,300,000

Issue Date FY: 2017 ( Subtotal = $2,300,000 )
2017	2017	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	4	8/10/2017	NON-COMPETING CONTINUATION	$2,185,000
2017	2017	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	001	4	9/22/2017	NON-COMPETING CONTINUATION	$115,000
														Subtotal = $2,300,000

Issue Date FY: 2016 ( Subtotal = $2,162,000 )
2016	2016	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	3	8/5/2016	NON-COMPETING CONTINUATION	$2,162,000
														Subtotal = $2,162,000

Issue Date FY: 2015 ( Subtotal = $2,185,000 )
2015	2015	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	2	8/20/2015	NON-COMPETING CONTINUATION	$2,185,000
														Subtotal = $2,185,000

Issue Date FY: 2014 ( Subtotal = $2,162,000 )
2014	2014	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	1	9/16/2014	NEW	$2,162,000
														Subtotal = $2,162,000

Grand Total All Awards = $10,959,497

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SPORE in Skin Cancer

Award Number: P50CA174523

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/16/2014

PERIOD OF PERFORMANCE END DATE: 08/31/2021

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