Marco Soster

Publications (2)8.36 Total impact

• Article: Antitumor activity of Src inhibitor saracatinib (AZD-0530) in preclinical models of biliary tract carcinomas.

  Giuliana Cavalloni, Caterina Peraldo-Neia, Ivana Sarotto, Loretta Gammaitoni, Giorgia Migliardi, Marco Soster, Serena Marchiò, Massimo Aglietta, Francesco Leone
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  ABSTRACT: Biliary tract carcinoma (BTC) has a poor prognosis due to limited treatment options. There is, therefore, an urgent need to identify new targets and to design innovative therapeutic approaches. Among potential candidate molecules, we evaluated the nonreceptor tyrosine kinase Src, observing promising antitumor effects of its small-molecule inhibitor saracatinib in BTC preclinical models. The presence of an active Src protein was investigated by immunohistochemistry in 19 surgical samples from patients with BTC. Upon saracatinib treatment, the phosphorylation of Src and of its downstream transducers was evaluated in the BTC cell lines TFK-1, EGI-1, HuH28, and TGBC1-TKB. The effect of saracatinib on proliferation and migration was analyzed in these same cell lines, and its antitumor activity was essayed in EGI-1 mouse xenografts. Saracatinib-modulated transcriptome was profiled in EGI-1 cells and in tumor samples of the xenograft model. Src was activated in about 80% of the human BTC samples. In cultured BTC cell lines, low-dose saracatinib counteracted the activation of Src and of its downstream effectors, increased the fraction of cells in G(0)-G(1) phase, and inhibited cell migration. At high concentrations (median dose from 2.26-6.99 μmol/L), saracatinib was also capable of inhibiting BTC cell proliferation. In vivo, saracatinib treatment resulted in delayed tumor growth, associated with an impaired vascular network. Here, we provide a demonstration that the targeted inhibition of Src kinase by saracatinib is of therapeutic benefit in preclinical models of BTC. We propose our results as a basis for the design of saracatinib-based clinical applications.
  Molecular Cancer Therapeutics 03/2012; 11(7):1528-38. · 5.23 Impact Factor
• Article: Targeted dual-color silica nanoparticles provide univocal identification of micrometastases in preclinical models of colorectal cancer.

  Marco Soster, Riccardo Juris, Sara Bonacchi, Damiano Genovese, Marco Montalti, Enrico Rampazzo, Nelsi Zaccheroni, Paolo Garagnani, Federico Bussolino, Luca Prodi, Serena Marchiò
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  ABSTRACT: Despite the recent introduction of targeted bio-drugs, the scarcity of successful therapeutic options for advanced colorectal cancer remains a limiting factor in patient management. The efficacy of curative surgical interventions can only be extended through earlier detection of metastatic foci, which is dependent on both the sensitivity and specificity of the diagnostic tools. We propose a high-performance imaging platform based on silica-poly(ethylene glycol) nanoparticles doped with rhodamine B and cyanine 5. Simultaneous detection of these dyes is the basis for background subtraction and signal amplification, thus providing high-sensitivity imaging. The functionalization of poly(ethylene glycol) tails on the external face of the nanoparticles with metastasis-specific peptides guarantees their homing to and accumulation at target tissues, resulting in specific visualization, even of submillimetric metastases. The results reported here demonstrate that our rationally designed modular nanosystems have the ability to produce a breakthrough in the detection of micrometastases for subsequent translation to clinics in the immediate future.
  International Journal of Nanomedicine 01/2012; 7:4797-807. · 3.13 Impact Factor