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Maximizing the use of a first clinically viable MYC inhibitor

Project description

Targeting the MYC oncogene

MYC is a family of regulator genes and proto-oncogenes that play crucial roles in cell cycle progression, apoptosis, and cellular transformation. Overexpression or amplification of MYC is observed in many types of cancers, leading to uncontrolled cell proliferation and tumour development. Although MYC genes are significant targets for therapeutic intervention, no MYC inhibitor has reached clinical approval. Funded by the European Research Council, the MYCiMAX project focuses on Omomyc, the first MYC-inhibiting mini-protein to complete a Phase I clinical trial. Researchers will explore the efficacy of Omomyc in brain malignancies and combine it with other inhibitors to study MYC's role in DNA damage response and oncogene cooperation.

Objective

Even though the MYC oncogene is a “most-wanted” target in cancer therapy, no MYC inhibitor has yet reached clinical approval. The applicant has developed Omomyc, the first MYC-inhibiting mini-protein to have successfully completed a Phase Ia clinical trial. The goal of this proposal is to maximise the use of this compound, as both a therapeutic and study tool, opening new lines of research in different aspects of MYC biology.
To start with, since Omomyc cannot efficiently cross the blood brain barrier, excluding it from use in brain malignancies or brain metastases, in Aim 1, we propose to validate its efficacy when delivered intracranially by different means, including osmotic pumps and hydrogels, as well as to test its delivery by intracarotid injection, in glioblastoma and brain metastases.
Then, in Aim 2 and 3, we will explore its combination with personalized medicine, namely PARPi and KRASi, respectively. These 2 aims are derived from two pillars of MYC biology: its role in DNA damage response and the paradigm of oncogene cooperation. Aim 2 will allow us to shed light on the role of MYC in homologous recombination and resistance to PARPi, while Aim 3 will deliver on the molecular mechanisms underlying the cooperation of RAS and MYC in multiple tumour types, where their combined inhibition could represent an unprecedented therapeutic opportunity.
Finally, Aim 4 will focus on the characterisation of cancers such as Small Cell Lung Cancer and Gastrointestinal Stromal Tumours that have the peculiarity of being defective for MAX – MYC’s natural partner – but that recapitulate a MYC-dependent tumour phenotype, likely driven by other members of the MYC network, whose function could also be hindered by Omomyc treatment.
Notably, each of the aims explores new aspects of MYC biology, tracing new lines of research around the most deregulated oncogene in human tumours as well as having immediate translational applicability in upcoming clinical trials of Omomyc.

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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-ADG

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Host institution

FUNDACIO PRIVADA INSTITUT D'INVESTIGACIO ONCOLOGICA DE VALL-HEBRON (VHIO)
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.

€ 2 499 904,00
Address
CALLE NAZARET 115-117
08035 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
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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.

€ 2 499 904,00

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