A new-generation drug capable of selectively attacking cancer cells. has been successfully tested in animal models by an international research team that also included scholars from the University of Bologna and the IRCCS Sant’Orsola Polyclinic. The findings —published inNature Communications – show complete regression of the disease in animal models of neuroblastoma and rhabdomyosarcoma, two rare childhood cancers, and also in colon cancer.
“These results pave the way for new clinical studies, with the aim of developing next-generation therapies that are more targeted and effective and can defeat rare tumours that are still resistant to currently available treatments,” says Mattia Lauriola, Professor of Histology at the University of Bologna’s Department of Medical and Surgical Sciences and among the authors of the study.
Antibody–drug conjugates are one of the most advanced frontiers in precision oncology. They combine the selectivity of antibodies with the targeted toxicity of a chemotherapeutic molecule, which is delivered only to the tumour cell recognised by the antibody.
In this way, the drug can locate, reach and attack only diseased cells, sparing healthy tissue. In animal models, this strategy led to complete tumour regression, which persisted even after treatment ended.
To achieve this level of selectivity, the team, led by researchers at the Children’s Hospital of Philadelphia, focused on a specific target: a receptor known as ALK. In several types of cancer, ALK is present in high amounts on the surface of tumour cells, while it is found only at low levels in healthy cells. This makes it an ideal candidate for targeted therapies.
The antibody–drug conjugate tested by the researchers was therefore developed specifically to recognise the ALK receptor and deliver the chemotherapeutic payload exclusively to cells that express it.
“Our analyses confirmed that the ALK protein is a very promising target against different forms of cancer, including colon cancer,” says Martina Mazzeschi, a researcher at the IRCCS Sant’Orsola Polyclinic. “While ALK was already a known target in neuroblastoma models, research carried out over the past five years suggests that ALK is also present in some subtypes of colon tumours.”
Both in vitro and in vivo tests therefore showed that an ALK-targeting antibody–drug conjugate can have an impact in models of neuroblastoma and rhabdomyosarcoma, as well as in colon cancer. This is particularly significant given that colon cancer is the second most commonly diagnosed cancer in Italy (in both men and women), with around 50,000 new cases each year.
“We are working to further optimise the identification of new targets that can be addressed by antibody–drug conjugates, in order to expand the number of solid tumours that can be treated while also mitigating resistance mechanisms,” adds Lauriola. “The hope is that this ‘precision chemotherapy’ could, where possible, replace traditional forms of chemotherapy.”
The study was published in Nature Communications under the title: “A humanized anaplastic lymphoma kinase (ALK)-directed antibody-drug conjugate with pyrrolobenzodiazepine payload demonstrates efficacy in ALK-expressing cancers.” For the University of Bologna and the IRCCS Sant’Orsola Polyclinic, Mattia Lauriola and Martina Mazzeschi took part in the study.
