PI: Dr. Emilia Migliano

The project aims to enhance the value of an active compound, cantharidin, produced by Meloidae beetles, which has garnered significant global medical interest (Fratini et al., 2021; Muzzi et al., 2022, 2020). Historically, its therapeutic properties have been known, primarily as an aphrodisiac and anti-inflammatory, and also for the treatment of warts, rabies, and cancer. However, its use has always been limited due to its high toxicity (Fratini et al., 2022). Although cantharidin is produced and marketed for dermatological use (e.g., as “Cantharone”), it does not have full FDA approval due to its high toxicity (LD50 = 0.03–0.5 mg/kg in humans) (Eichenfield et al., 2021). If accidentally ingested, the substance causes severe gastrointestinal and urinary trauma. For this reason, topical application of existing cantharidin-based drugs is only allowed in clinical trials, conducted by specialized physicians under strict procedural constraints.

To overcome these limitations and enable broader use of cantharidin-based dermatological and oncological products, an efficient targeted drug-delivery system must be developed to control its release or otherwise minimize side effects in non-pathological tissues (Chau et al., 2019; Li et al., 2023).

Project Start Date: 10/12/2024
Project End Date: 31/10/2025

The main goal of this proposal is to analyze the cellular mechanisms underlying the cytotoxic effects of cantharidin in different types of cutaneous tumor cells. In particular, the project focuses on skin cancers derived from keratinocytes (non-melanoma skin cancer; NMSC) and melanocytes (melanoma), which are among the most common malignant tumors worldwide.

The final objective is to design and test one or more cantharidin-conjugated antibodies (Antibody-Drug Conjugates, ADCs) targeting specific surface markers on tumor cells, in order to selectively deliver the toxic compound to cancer cells only.