Summary
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.
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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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101142260 |
| Start date: | 01-05-2024 |
| End date: | 30-04-2029 |
| Total budget - Public funding: | 2 499 904,00 Euro - 2 499 904,00 Euro |
Cordis data
Original description
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.
Status
SIGNEDCall topic
ERC-2023-ADGUpdate Date
19-12-2024
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