Role of Autophagy and Lysosomes in Tumorigenesis and their Potential as Therapeutic Targets

We will continue our efforts to identify and characterize commonly used drugs to target cellular recycling machineries in innovative cancer treatment.

We have shown that cationic amphiphilic drugs (CADs: e.g. antihistamines Ebastine and Loratadine) and disulfiram (also known as Antabuse) are potent anti-cancer agents that target cancer cell lysosomes and the proteasome pathway, respectively. While we are preparing clinical trials to test their efficacy in cancer treatment, we will continue our mechanistic and pharmacological research efforts to ensure their optimal development in the clinics.

Repurposing cationic amphiphilic drugs (CADs) for cancer therapy

Lysosomes activated during malignant transformation are characterized by reduced lysosomal membrane stability, thereby sensitizing cells to lysosome-dependent cell death that can be induced by CADs. We will investigate molecular mechanisms of action of CADs with particular focus on their inhibitory effect on lysosomal lipases and their cancer specificity to develop optimal CADs for future cancer therapy. 

Exploring Antabuse and its derivatives to combat drug-resistant, metastatic cancer

We have previously identified, synthesised and validated the active anti-cancer metabolite of disulfiram (DSF), the dithiocarb-copper complex (CuET), that effectively kills cancer cells by targeting the proteasome pathway. We will explore mechanistic details of the CuET interaction with its targets, elucidate cancer cells’ pathway(s) most vulnerable to CuET treatment, and develop and validate candidate biomarkers to guide treatment by DSF/CuET.