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Co-option of host circadian rhythms in cancer

Project description

Decoding the biological clock of cancer

The immune system plays a crucial role in recognising and eliminating abnormal cells, including those that could become cancerous, using specific immune surveillance mechanisms. However, tumours employ various strategies to evade immune detection. Understanding these interactions is crucial for developing immunotherapies that enhance and harness the power of the immune system to combat cancer effectively. Funded by the European Research Council, the INN-TIME project aims to investigate how tumours manipulate host circadian rhythms (CRs), natural, internal processes that repeat roughly every 24 hours and help organisms adjust to a changing environment. Researchers will study CRs in lung cancer and develop strategies to eliminate such processes that support tumour growth.

Objective

Circadian rhythms (CRs) are the biological response to the periodic rotations of the Earth, and allow
fundamental adaptations of organisms to a changing environment. CRs are molecularly controlled in every cell
by a set of transcriptional factors that control, and are influenced by, core biological processes including
metabolic, immune, and proliferative.
My previous studies established, for the first time, that innate immune cells regulate the circadian physiology
of tissues, including the susceptibility of the lung to be metastasized. In INN-TIME, I ask the reciprocal
question to reveal if tumors take advantage of, and subvert, CRs of the innate (immune and stroma)
compartments to escape anti-tumoral defense. INN-TIME Aims to understand how oncogenic processes
rewire CRs of the host and to elucidate strategies that halt this subversion as a new approach to fight
cancer. Using lung cancer as proof-of-principle, I will first investigate cell-intrinsic circadian programs in
tumors (Aim1). Next, I will define how tumors co-opt circadian clocks of the host and explore how the
molecular clock of innate immune (Aim2) and supporting stromal cells (Aim3) impacts tumor growth, both
molecularly and functionally. By integrating multiple transcriptomics and functional approaches, INN-TIME
will discover novel regulatory programs in tumors using a circadian approach, and pave the way to design
strategies to prevent cancer by interfering with tumor-supportive circadian programs.
INN-TIME will revolutionize the way we understand cancer, as it will identify the malignant roots of
circadian rhythms and their impact on host defense. This research will establish a new paradigm by revealing
the mechanisms underlying pro-tumorigenic clocks, and will provide robust foundations for new therapies
in a set of disorders in which circadian clock (dys)functions are implicated.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-STG

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Host institution

FUNDACION SECTOR PUBLICO ESTATAL CENTRO NACIONAL INVESTIGACIONES ONCOLOGICAS CARLOS III
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 500 000,00
Address
C MELCHOR FERNANDEZ ALMAGRO 3
28029 Madrid
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 500 000,00

Beneficiaries (1)

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