Project description
Novel drug targets for breast cancer metastasis
Breast cancer metastasis is a critical aspect of the disease, involving the spread of cancer cells from the primary tumour site in the breast to distant organs or tissues in the body. Funded by the European Research Council, the Metalron project focuses on a solute carrier (SLC) transporter that plays a crucial role in breast cancer cell metastasis to the lungs and liver. The study will investigate SLC function in various types of cancer and evaluate the efficacy of anti-sense oligonucleotides against the transporter and small molecule inhibitors in disease models. Results will likely identify novel drug targets and open new avenues for metastasis treatment.
Objective
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.
Fields of science
Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-ERC-POC - HORIZON ERC Proof of Concept GrantsHost institution
9052 ZWIJNAARDE - GENT
Belgium