Targeting Mfrn2 to Inhibit Metastatic Cancers

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, wehypothesize 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 inhibitionbeyond 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.