Drug Repurposing
Patients with brain metastases (BM) face a poor prognosis, and current treatment options remain largely ineffective. No drugs specifically targeting BM are available. The delivery of novel therapies, such as targeted agents and immunotherapies, is further complicated by the blood-brain barrier (BBB), which remains largely intact during the early stages of BM development. Therefore, there is a critical need for drugs capable of penetrating an uncompromised BBB.
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Our previous work has demonstrated that certain antipsychotic drugs can cross an intact BBB and inhibit the development of melanoma BM in animal models. We now have compelling evidence showing that the antipsychotic medications trifluoperazine (external link), clozapine (external link), and thioridazine significantly inhibit the progression of melanoma BM. This project brings together research groups with strong expertise in medicinal chemistry and drug development alongside our team, which has established advanced BM model systems.
To date, we have synthesized and tested new analogues of clozapine and conducted extensive screening of these compounds using our human BM model systems, including cell lines and brain organoids. Our ongoing work holds promise for the development of novel therapeutic strategies to improve outcomes for patients suffering from BM, who currently have very limited treatment options.