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PROMINENT - IARC

Award Number: OT2CA278681
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: OTHER
PERIOD OF PERFORMANCE START DATE: 06/22/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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PROMINENT - IARC - The cancer research community is on the verge of a major leap in our understanding of the factors that contribute to human cancer risk. While it is clear that mutations in DNA, either spontaneous or environmentally induced, are essential for cancer development, recent advances have highlighted the importance of non-mutagenic factors as rate-limiting determinants of cancer risk in human populations and in mouse cancer models. The root causes of human cancer have been widely debated, but most of the emphasis has been on the origins of the “driver” mutations that are ubiquitous in human tumours. Although epidemiology studies have highlighted the possible roles of lifestyle factors such as obesity, alcohol consumption, inflammation and poor diet in cancer risk, it has generally been assumed that these factors act directly or indirectly to cause mutations in DNA, thus contributing to tumour mutational burden and resulting in increased cancer risk. In contrast, recent sequencing studies have uncovered abundant mutations in normal human tissues, suggesting that even strong cancer driver mutations are not sufficient for cancer formation. These results were presaged by studies of mouse tumour models, some carried out more than 50 years ago, showing that promotion is the rate-limiting step in tumour development. To identify the mechanisms that control mutated normal cells, and to elucidate the precise mechanisms by which promoting factors stimulate the conversion of these cells to neoplastic growth, we have assembled a multidisciplinary team of investigators with wide-ranging experience in epidemiology, genetics, computational network analysis and machine learning, tissue imaging of gene expression, single cell transcriptomics, and genome-wide CRISPR functional screens. We will focus human analysis on a unique collection of several thousand human normal and matched tumour samples from >20 countries, including regions of both high and low cancer risk. Detailed risk factor information and whole genome sequence data is available from all these samples as part of the Grand Challenge Mutographs study. Analysis of these samples, together with detailed intervention studies in human populations, mouse models and human organoids, will allow us to develop a roadmap of tumour promotion from single normal cells carrying driver mutations, through to malignant progression. Our findings will facilitate identification of the causative environmental factors that promote cancer and provide routes to new methods and approaches to cancer prevention based on a deeper understanding of the process of initiated cell selection by tumour promoting agents.


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: 2025 ( Subtotal = $0 )
2025	2022	CENTRE INTERNATIONAL DE RECHERCHE SUR LE CANCER	25 AVE TONY GARNIER	LYON				FRA	Cancer Cause and Prevention Research	000	1	5/7/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $502,922 )
2024	2024	CENTRE INTERNATIONAL DE RECHERCHE SUR LE CANCER	25 AVE TONY GARNIER	LYON				FRA	Cancer Cause and Prevention Research	002	1	9/13/2024	SUPPLEMENT FOR EXPANSION	$33,503
2024	2024	CENTRE INTERNATIONAL DE RECHERCHE SUR LE CANCER	25 AVE TONY GARNIER	LYON				FRA	Cancer Cause and Prevention Research	001	1	9/5/2024	SUPPLEMENT FOR EXPANSION	$469,419
2024	2022	CENTRE INTERNATIONAL DE RECHERCHE SUR LE CANCER	25 AVE TONY GARNIER	LYON				FRA	Cancer Cause and Prevention Research	000	1	6/6/2024	NEW	$0
														Subtotal = $502,922

Issue Date FY: 2023 ( Subtotal = $450,879 )
2023	2023	CENTRE INTERNATIONAL DE RECHERCHE SUR LE CANCER	25 AVE TONY GARNIER	LYON				FRA	Cancer Cause and Prevention Research	001	1	8/4/2023	SUPPLEMENT FOR EXPANSION	$450,879
2023	2022	CENTRE INTERNATIONAL DE RECHERCHE SUR LE CANCER	25 AVE TONY GARNIER	LYON				FRA	Cancer Cause and Prevention Research	000	1	5/26/2023	NEW	$0
														Subtotal = $450,879

Issue Date FY: 2022 ( Subtotal = $391,529 )
2022	2022	CENTRE INTERNATIONAL DE RECHERCHE SUR LE CANCER	150 COURS ALBERT THOMAS	LYON				FRA	Cancer Cause and Prevention Research	000	1	6/22/2022	NEW	$391,529
														Subtotal = $391,529

Grand Total All Awards = $1,345,330

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PROMINENT - IARC

Award Number: OT2CA278681

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: OTHER

PERIOD OF PERFORMANCE START DATE: 06/22/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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