Centro Interdipartimentale di Biotecnologie Molecolari "Guido Tarone"
Roberto Chiarle e Claudia Voena PI
- Cristina Mastini Senior Technician
- Vera Mugoni Senior Researcher
- Dominik-Laurentius Candea PhD student in Molecular Medicine, MSCA – DN
- Maria Vittoria Di Marco PhD student in Molecular Medicine
- Alessandro Gasparetto MD PhD student in Biomedical Sciences and Oncology
Monica Maccagno PhD student in Biomedical Sciences and Oncology - Marta Rubin PhD student in Molecular Medicine
Mariapia Russo PhD student in Biomedical Sciences and Oncology - Roberta Tagliero PhD student in Biomedical Sciences and Oncology
- Gloria Arena Postgraduate Fellow
- Andrea Macioce Postgraduate Fellow
- Francesca Pancioni Graduate Student
- Alice Pistone Graduate Student
Research activity
Several hematological and solid tumors display genetic alterations in the gene encoding Anaplastic Lymphoma Kinase (ALK) (Figure 1).
ALK rearrangements define a distinct molecular subset of non-Hodgkin T cell lymphoma, namely Anaplastic Large Cell Lymphoma (ALCL), and non-small cell lung cancer (ALK+ NSCLC), whereas ALK activating single point mutations characterize neuroblastoma (NB). ALK chromosomal rearrangements involve different partner genes and result in fusion genes that encode for new oncogenic chimeric proteins, such as NPM-ALK in ALCL and EML4-ALK in NSCLC. ALK fusion proteins are constitutively active and contribute to tumorigenesis and maintenance of neoplastic phenotype. ALK-rearranged tumors are totally dependent on ALK activity, making ALK an attractive target for therapy. Different ALK tyrosine kinase inhibitors (TKIs), crizotinib, ceritinib, brigatinib, alectinib and lorlatinib, have been developed and FDA approved for treatment of ALK+ NSCLC in first and second-line treatment. Crizotinib has been recently approved for refractory/relapsed ALK+ ALCL and ALK TKIs are currently evaluated in several clinical trials for different ALK-driven tumors. Overall, ALK TKIs have revolutionized the therapeutic opportunities of ALK-driven tumors. Nonetheless, the development of resistance limits their long-term clinical impact. We have extensively studied the role of ALK in lymphoma and in lung cancer using in vitro and in vivo models. Our lab aims at discovering the key mechanisms of ALK-mediated transformation and resistance to therapy while developing therapeutic approaches to completely eradicate ALK-positive cancers.
