Melanoma Research Team

The Melanoma Research Team is translational research oriented and applies cell and molecular biology-based techniques alongside in vivo approaches to exploit new therapies in preclinical settings.

Melanoma is the deadliest skin cancer and extremely difficult to treat when disease recurs.

Although melanoma is curable in the early stages, metastatic melanoma continues to be a therapeutic challenge due to the development of therapy resistance. However, a remarkable improvement in the survival of patients with advanced melanoma has been achieved by the clinical employment of i) kinase inhibitors in BRAF/RAS-mutated patients (Targeted Therapy) and ii) immune-checkpoint inhibitors (Immune Therapy).

The main focus of our research is

• to dissect the molecular mechanisms underlying the biology of melanoma by means of multi-level approaches (e.g., cell- and animal-based systems; computational tools)
• to in vivo exploit new therapies, in combination or not with current melanoma therapies, as preclinical settings before clinical trials

One of our main goals is to understand the metabolic heterogeneity of melanoma. In particular, we aim at finding new molecular players of metabolic rewiring in melanoma and identify new drug candidates to apply in melanoma therapy (in collaboration with Prof. Thomas Sauter, Luxembourg University).

In addition, we seek to find new therapeutic strategies in combination with immunotherapy, focusing on increasing the efficacy of immune checkpoints inhibitors. To this aim, we work in close collaboration with the Rigshospitalet (Prof. Kjeld Schmiegelow), Copenhagen University and Herlev Hospital (Center for Cancer Immune Therapy) in Copenhagen. 

Selected publications:

Nazerai L, Willis SC, Yankilevich P, Di Leo L, Bosisio FM, Frias A, Bertolotto C, Nersting J, Thastrup M, Buus S, Thomsen AR, Nielsen M, Rohrberg KS, Schmiegelow K, De Zio D: Thiopurine 6TG treatment increases tumor immunogenicity and response to immune checkpoint blockade. Oncoimmunology 2023;12:2158610

Pagliuca C, Di Leo L, De Zio D: New Insights into the Phenotype Switching of Melanoma. Cancers (Basel) 2022;14:6118

Tiberti M, Di Leo L, Vistesen MV, Kuhre RS, Cecconi F, De Zio D*, Papaleo E*: The Cancermuts software package for the prioritization of missense cancer variants: a case study of AMBRA1 in melanoma. Cell Death Dis  2022;13:872. * Co-last authors

Di Leo L, Bodemeyer V, Bosiso FM, Claps G, Carretta M, Rizza S, Faienza F, Frias A, Khan S, Bordi M, Pacheco MP, Di Martino J, Bravo-Cordero JJ, Daniel CJ, Sears RC, Donia M, Madsen DH, Guldberg P, Filomeni G, Sauter T, Robert C,  De Zio D^*, Cecconi F^*: Loss of Ambra1 promotes melanoma growth and invasion. Nat Commun 2021; May 5. ^* Co-last authors

Maiani E, Milletti G, Nazio F, Holdgaard SG, Bartkova J, Rizza S, Cianfanelli V, Lorente M, Simoneschi D, Di Marco M, D'Acunzo P, Di Leo L, Rasmussen R, Montagna C, Raciti M, De Stefanis C, Gabicagogeascoa E, Rona G, Salvador N, Pupo E, Merchut-Maya JM, Daniel CJ, Carinci M, Cesarini V, O'sullivan A, Jeong YT, Bordi M, Russo F, Campello S, Gallo A, Filomeni G, Lanzetti L, Sears RC, Hamerlik P, Bartolazzi A, Hynds RE, Pearce DR, Swanton C, Pagano M, Velasco G, Papaleo E, De Zio D, Maya-Mendoza A, Locatelli F, Bartek J, Cecconi F: AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity. Nature 2021; April 14