A central problem of oncology is represented by the fact that the most molecularly targeted anticancer drugs produce only transient therapeutic effects due to the clonal selection of drug-resistant tumor cells.

Current studies

Our projects are oriented to the development of experimental models able to recapitulate in vitro and in vivo the complexity of the mechanisms underlying the process of tumor evolution and the development of drug resistance. By using a combination of biochemistry, molecular and cellular biology approaches as well as preclinical in vivo models, the current projects are aimed at gaining insight into the general mechanisms of cell transformation and to develop tumor-specific therapies based on "synthetic lethality".

One of the key hallmarks of cancer cells is sustained growth, which require a complex metabolic rewiring with an enhancement of anabolic pathways and a profound alteration of redox homeostasis. In particular, we focus on genetic and pharmacological approaches that modify the metabolic profile and redox homeostasis of cancer cells to trigger their response to pro-apoptotic stimuli.

5 selected publications

• Silic-Benussi M, Sharova E, Ciccarese F, Cavallari I, Raimondi V, Urso L, Corradin A, Kotler H, Scattolin G, Buldini B, Francescato S, Basso G, Minuzzo SA, Indraccolo S, D'Agostino DM, and Ciminale V. mTOR inhibition downregulates glucose-6-phosphate dehydrogenase and induces ROS-dependent death in T-cell acute lymphoblastic leukemia cells. Redox Biol. 2022;51:102268. doi: 10.1016/j.redox.2022.102268. PMID: 35248829.
• Raimondi V, Ciccarese F, Ciminale V. Oncogenic pathways and the electron transport chain: a dangeROS liaison. Br J Cancer. 2020; 122:168-181. doi: 10.1038/s41416-019-0651-y. PMID:31819197.
• Silic-Benussi M, Scattolin G, Cavallari I, Minuzzo S, del Bianco P, Francescato S, Basso G, Indraccolo S, D’Agostino DM and Ciminale V. Selective killing of human T-ALL cells: an integrated approach targeting redox homeostasis and the OMA1/OPA1 axis. Cell Death and Disease, 2018; 9:822. doi: 10.1038/s41419-018-0870-9.
• Silic-Benussi M, Cavallari I, Vajente N, Vidali S, Chieco-Bianchi L, Di Lisa F, Saggioro D, D’Agostino DM and Ciminale V. (2010) Redox regulation of T-cell turnover by the p13 protein of human T-cell leukemia virus type 1: distinct effects in primary vs. transformed cells. Blood, 116:54-62.

• Urso L, Cavallari I, Sharova E, Ciccarese F, Pasello G, Ciminale V. Metabolic rewiring and redox alterations in malignant pleural mesothelioma. Br J Cancer. 2020; 122:52-61. doi: 10.1038/s41416-019-0661-9.

Funding
AIRC
Istituto Oncologico Veneto 5 x 1000

Personnel involved
Vincenzo Ciminale, Full Professor

Group members
Ilaria Cavallari, Postdoctoral Fellow
Micol Silic-Benussi, Postdoctoral Fellow
Loredana Urso Postdoctoral Fellow
Vittoria Raimondi Postdoctoral Fellow
Francesco Ciccarese, Postdoctoral Fellow
Evgenyia Sharova, Postdoctoral Fellow
Irene Bertazzolo, Ph.D. Student
Arezoo Darbandi, Ph.D. Student