The experimental anti-cancer platinum drug Ptac2S has higher anti-cancer activity than standard of care cisplatin in malignant pleural mesothelioma (MPM) cells, researchers reported, a preclinical finding that suggests it may be a promising candidate for treatment-resistant MPM.
The study, “In Vitro And In Vivo Antitumor Activity Of [Pt(O,O′-Acac)(Γ-Acac)(DMS)] In Malignant Pleural Mesothelioma,” was published in PLoS One, and conducted by researchers at the University of Salento, in Italy.
“MPM is a clinical challenge because its incidence increases, and is expected to rise further due to the widespread use of asbestos in diverse developing nations,” the researchers wrote. “The most effective treatment proven to prolong life of malignant mesothelioma patients is the combination of multi-folate inhibitors, pemetrexed or raltitrexed and cisplatin (CDDP), but still the median survival is only 12 months, and response rates are approximately 40%.”
For these reasons, “attention was paid to the design of new platinum compounds with stronger pharmacological properties, less toxicity and more favourable therapeutic indices equated to CDDP,” they said.
Ptac2S is a platinum drug that is gaining attention due to its antiproliferative activity and reduced toxicity, observed in a breast cancer cell line and in animal models. Unless cisplatin, this drug does not affect the cell’s DNA, making it less likely to induce resistance to therapy.
To understand whether Ptac2S could destroy resistant MPM cells, researchers compared its effect with that of cisplatin in animal models and in commercially available human MPM cells, originally obtained from asbestos-exposed patients.
Results showed that Ptac2S was significantly more toxic (about 12 times more) to MPM cells than cisplatin. It was also more effective than cisplatin in inducing cell death mechanisms within MPM cells by affecting their ability to produce energy to survive and by increasing the expression of proteins that activate cell death, such as the p38 signaling pathway. Consistent with such findings, Ptac2S was also more efficient than cisplatin in reducing tumor volume in mice with MPM.
“Altogether, our results confirm that Ptac2S is a promising therapeutic agent for malignant mesothelioma, providing a solid starting point for its validation as a suitable candidate for further pharmacological testing,” the researchers concluded.