Summary
Metastasis formation is the leading cause of death in cancer patients. Thus, there is an unmet need for
drugs that can prevent and/or treat systemic metastases. We have discovered that breast cancer cells rely
on a solute carrier (SLC) transporter for metastasis formation in lung and liver. Interestingly, systemic
inhibition of this SLC transporter using a therapeutic modality has likely a favorable toxicity profile
because knockout mice are viable and have very few and minor phenotypic changes. Therefore, we
hypothesize that targeting the SLC transporter can be exploited to inhibit metastatic growth. To valorize
this SLC transporter as a drug target, we will 1. Perform a detailed mechanistic analysis of its function
in samples from breast cancer patients; 2. Define the efficacy profile of the inhibition of this SLC
transporter against systemic metastasis in mouse models; 3. Translate the SLC transporter inhibition
beyond breast cancer; 4. Determine the efficacy and safety of targeting metastatic patient-derivedxenograft (PDX) with anti-sense oligonucleotides (ASOs) against this SLC transporter and 5. Delineate
a strategy to define small molecule inhibitors against the SLC transporter. To do so, we will apply
multiplex immunohistochemistry in samples from breast cancer patients and perform state-of-the-art
metastasis assays in allograft, xenograft and PDX mouse models. Thus, we will deliver a comprehensive
evaluation of the SLC transporter as drug target for treating metastases.
drugs that can prevent and/or treat systemic metastases. We have discovered that breast cancer cells rely
on a solute carrier (SLC) transporter for metastasis formation in lung and liver. Interestingly, systemic
inhibition of this SLC transporter using a therapeutic modality has likely a favorable toxicity profile
because knockout mice are viable and have very few and minor phenotypic changes. Therefore, we
hypothesize that targeting the SLC transporter can be exploited to inhibit metastatic growth. To valorize
this SLC transporter as a drug target, we will 1. Perform a detailed mechanistic analysis of its function
in samples from breast cancer patients; 2. Define the efficacy profile of the inhibition of this SLC
transporter against systemic metastasis in mouse models; 3. Translate the SLC transporter inhibition
beyond breast cancer; 4. Determine the efficacy and safety of targeting metastatic patient-derivedxenograft (PDX) with anti-sense oligonucleotides (ASOs) against this SLC transporter and 5. Delineate
a strategy to define small molecule inhibitors against the SLC transporter. To do so, we will apply
multiplex immunohistochemistry in samples from breast cancer patients and perform state-of-the-art
metastasis assays in allograft, xenograft and PDX mouse models. Thus, we will deliver a comprehensive
evaluation of the SLC transporter as drug target for treating metastases.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101112780 |
| Start date: | 01-06-2023 |
| End date: | 30-11-2024 |
| Total budget - Public funding: | - 150 000,00 Euro |
Cordis data
Original description
Metastasis formation is the leading cause of death in cancer patients. Thus, there is an unmet need fordrugs that can prevent and/or treat systemic metastases. We have discovered that breast cancer cells rely
on a solute carrier (SLC) transporter for metastasis formation in lung and liver. Interestingly, systemic
inhibition of this SLC transporter using a therapeutic modality has likely a favorable toxicity profile
because knockout mice are viable and have very few and minor phenotypic changes. Therefore, we
hypothesize that targeting the SLC transporter can be exploited to inhibit metastatic growth. To valorize
this SLC transporter as a drug target, we will 1. Perform a detailed mechanistic analysis of its function
in samples from breast cancer patients; 2. Define the efficacy profile of the inhibition of this SLC
transporter against systemic metastasis in mouse models; 3. Translate the SLC transporter inhibition
beyond breast cancer; 4. Determine the efficacy and safety of targeting metastatic patient-derivedxenograft (PDX) with anti-sense oligonucleotides (ASOs) against this SLC transporter and 5. Delineate
a strategy to define small molecule inhibitors against the SLC transporter. To do so, we will apply
multiplex immunohistochemistry in samples from breast cancer patients and perform state-of-the-art
metastasis assays in allograft, xenograft and PDX mouse models. Thus, we will deliver a comprehensive
evaluation of the SLC transporter as drug target for treating metastases.
Status
SIGNEDCall topic
ERC-2022-POC2Update Date
31-07-2023
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