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Project ILLUMINE - Exploiting the Dark Proteome to fight cancer

Award Number: OT2CA321158
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: OTHER
PERIOD OF PERFORMANCE START DATE: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Project ILLUMINE - Exploiting the Dark Proteome to fight cancer - ABSTRACT Cells produce a previously under-appreciated class of non-standard proteins collectively termed the dark proteome that are not encoded by known open reading frames or explained by DNA mutations. The biological origins, regulation and functional role of the dark proteome in normal tissues and cancer remains largely unknown. This challenge aims to uncover the mechanisms that give rise to dark proteome products and to define their connection to the oncogenic state. Team ILLUMINE led by Reuven Agami (Netherlands Cancer Institute) brings together interdisciplinary researchers with expertise in cancer biology, proteomics, genomics, chemistry, technology development and clinical translation. The program will address four central questions: who the dark proteome players are, whether and how they are (dys)regulated in cancer, how they function, and how they can be therapeutically exploited. In addressing these questions, ILLUMINE will address major gaps in knowledge. Aim 1 will create a comprehensive map of dark proteome entities across several major cancer types and dissect potential stress-related mechanisms for their production. Aim 2 will codify a bench-to-bedside pre-clinical therapeutic development pipeline for immunotherapies from the dark proteome. Aim 3 will profile cell-based mechanisms of individual dark proteins in cancer biology, focusing on cell autonomous and non-cell autonomous mechanisms. Aim 4 will explore non- immunotherapy opportunities for targeting the dark proteome. Capitalizing on its unique expertise the team plans to use and combine cutting-edge experimental approaches to uncover hidden layers of cancer cell biology. ILLUMINE aims to ultimately identify new tumor biology and treatment paradigms for patients based on the dark proteome.


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: 2026 ( Subtotal = $571,255 )
2026	2026	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Cancer Cause and Prevention Research	000	1	8/5/2026	NEW	$571,255
														Subtotal = $571,255

Grand Total All Awards = $571,255

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Project ILLUMINE - Exploiting the Dark Proteome to fight cancer

Award Number: OT2CA321158

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: OTHER

PERIOD OF PERFORMANCE START DATE: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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