Improvement of cancer treatment is an urgent clinical need since cancer remains incurable in most cases due to drug resistance or advanced disease.

Alteration of iron balance potentially impacts proliferating and/or metabolically active cancer cells. Redox properties make iron both essential for biological processes and potentially a toxic element. Both iron starvation and excess ultimately leads to cell toxicity and death by limiting iron availability and promoting reactive oxygen species generation, respectively.

Several studies demonstrated that iron chelation inhibits cancer cell growth. However, this strategy has limited translational impact, since cancer patients often are or become anemic during disease progression.

Our studies focus on the role of iron in disease development, including anemia, in multiple myeloma and advanced prostate cancer with emphasis on the possibility to exploit iron excess to reduce disease progression and ameliorate pharmacological therapies.

Curriculum Vitae

From 2016:                 Senior scientist at the Regulation of Iron Metabolism Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.

From 2016:                 Tutor of the course “Molecular and cellular assays and bioimaging”, Faculty of Medicine, Vita-Salute San Raffaele University, Milan, Italy.

2012-2016:                 Adjunct Professor, course “Genetics and Developmental Biology ” and Tutor of the course “Molecular and cellular assays and bioimaging”, Faculty of   Medicine, Vita-Salute San Raffaele University, Milan, Italy.

From 2014:                 Member of the European Iron Club.

2010-2015:                 Post doctoral research fellow, San Raffaele Scientific Institute Milan, Italy.

2010:                          PhD degree in Molecular Medicine, Vita-Salute San Raffaele University, Milan, Italy.

2006-2010:                 PhD student fellow, Molecular Medicine PhD program, Vita-Salute San Raffaele University, Milan, Italy.

From 2005:                 Member of the International BioIron Society.

2000-2005:                 Graduate student fellow. San Raffaele Scientific Institute Milan, Italy.

2000:                          Master degree in Biological Science, Università degli Studi di Milano, Milan, Italy.

 

Financial support

2016-2018: Group Leader. AIRC 5×1000 Program Grant in Molecular Oncology-Extension Id: 9965

2015-2017: Principal Investigator. AIRC-Fondazione Cariplo TRIDEO 2014 Id. 15465

2013-2016: Co-PI. Ospedale San Raffaele, Ricerca Corrente, Linea di ricerca 6, WP3: Regolazione di epcidina nell’infiammazione neoplastica: il modello del mieloma multiplo. PI: Prof Clara Camaschella

 

Publications

Researcher unique identifier(s): Researcher ID: N-8315-2015

ORCID: 0000-0002-3463-1199

 

Number of peer reviewed publications: 25

Total citations: 932 (April, 2017)

Total Impact factor: 153

Scopus h-index: 16 (April, 2017)

research Activity

Our research group studies the role of iron and the effect of its manipulation in multiple myeloma cellular and murine models. Malignant plasma cells are potentially sensitive to iron toxicity since they generate high levels of hydrogen peroxide, as byproduct of antibody synthesis. Moreover, our preliminary data suggested that iron competition takes place in the local bone marrow microenvironment. Thus, we hypothesized that iron restriction in the tumor microenvironment favors both anemia and malignant PC survival and that disrupting this circuit by inducing a condition of iron excess may both improve anemia and limit disease progression. We evaluated also the effect of iron on bortezomib efficacy since this cytotoxic agent, commonly used to treat myeloma patients, perturbs cellular redox environment as a side effect of its activity. We found that induction of iron excess impairs myeloma cells proliferation and increases bortezomib efficacy both in vitro and in murine models, where iron and bortezomib were administered at human equivalent doses. Current experiments are ongoing in preclinical models to set up combination therapies including iron with the final aim to propose a pilot clinical study.

In parallel, we considered this strategy worth to be explored in malignancies other than multiple myeloma. We started from prostate cancer cells that genetically rearrange iron trafficking proteins as malignant myeloma cells to favor iron uptake and retention, an adaptation that favors proliferation under physiologic iron availability, but becomes an Achille’s hill in iron excess. In addition, as malignant plasma cells, also prostate cancer cells originate from specialized secretory cells and possibly are sensitive to bortezomib. Our preliminary results connect iron balance with androgen metabolism, a link we plan to explore in detail in our future experiments.

Selected Publications

  1. Bordini J, Galvan S, Ponzoni M, Bertilaccio MT, Chesi M, Bergsagel PL, Camaschella C, Campanella A. Induction of iron excess restricts malignant plasma cells expansion and potentiates bortezomib effect in models of multiple myeloma. Leukemia. 2017 Apr;31(4):967-970.

 

  1. Nai A, Rubio A, Campanella A, Gourbeyre O, Artuso I, Bordini J, Gineste A, Latour C, Besson-Fournier C, Lin HY, Coppin H, Roth MP, Camaschella C, Silvestri L, Meynard D. Limiting hepatic Bmp-Smad signaling by matriptase-2 is required for erythropoietin-mediated hepcidin suppression in mice. Blood. 2016 May 12;127(19):2327-36.

 

  1. Bordini J, Bertilaccio MT, Ponzoni M, Fermo I, Chesi M, Bergsagel PL, Camaschella C, Campanella A. Erythroblast apoptosis and microenvironmental iron restriction trigger anemia in the VK*MYC model multiple myeloma. Haematologica. 2015 Jun;100(6):834-841

 

  1. Campanella A, Santambrogio P, Fontana F, Frenquelli M, Cenci S, Marcatti M, Sitia R, Tonon G, and Camaschella C. Iron increases the susceptibility of Multiple Myeloma cells to bortezomib. Haematologica. 2013 Jun;98(6):971-9

 

  1. Corna G, Campana L, Pignatti E, Castiglioni A, Tagliafico E, Bosurgi L, Campanella A, Brunelli S, Manfredi AA, Apostoli P, Silvestri L, Camaschella C, Rovere-Querini P. Polarization dictates iron handling by inflammatory and alternatively activated macrophages. Haematologica. 2010;95(11):1814-22