Translational cancer research transforms new
knowledge obtained from basic research into innovative therapeutic and
diagnostic tools for cancer patients. The identification of molecular pathways and mechanisms playing a key role in
tumor growth and progression provided a number of new targets, potential probes
and drugs for diagnostic and therapeutic intervention in oncology. Molecular
imaging with its ability to evaluate in vivo complex biological processes such
as proliferation, apoptosis, angiogenesis, gene expression, receptor/ligand
interactions, transport of substrates and metabolism of nutrients in human
cancers can accelerate this transfer process. Imaging technologies such as
PET/CT and SPECT/CT can be employed in pre-clinical and clinical experimental
settings for visualization of target expression or function as well as
modulation of downstream pathway. In this framework our research activity is
focused on the development and characterization of new probes for imaging of
the expression of tumor targets or drug-induced modulation of downstream
pathways. To this end several tumor models are available in our laboratory in
order to test new tracers and drugs. In particular we characterized and
validated tracers for imaging of tumor proliferation, apoptosis and
angiogenesis and tested the effects of several tyrosine kinase inhibitors
(TKIs). For instance non-invasive imaging of proliferation with 18F-Fluorothymidine
(18F-FLT) and PET was used to detect MET-mediated resistance in non-small
cell lung cancer (NSCLC) and to monitor its reversal by MET inhibitors. We showed
that the persistently high uptake of 18F-FLT in tumors after
treatment with EGFR TKIs identified resistance whereas the significant
reduction of tracer uptake in response to treatment with MET inhibitors
indicated the reversal of MET-mediated resistance. The major clinical
implication of this study was to provide an adaptive imaging biomarker for
translational targeted therapy in NSCLC patients.
Figures:
Longitudinal imaging studies with 18F-FLT in H1993 xenografts
bearing MET amplification. The persistently high uptake of 18F-FLT
in tumors after treatment with erlotinib identified resistance whereas the
significant reduction of tracer uptake in response to MET TKI indicated the
reversal of MET-mediated resistance.
Selected papers:
Papers:
-Monitoring reversal of MET-mediated resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer using 3 '-deoxy-3 '-[18F]-fluorothymidine positron emission tomography. Iommelli F, De Rosa V, Gargiulo S, Panico M, Monti M, Greco A, Gramanzini M, Ortosecco G, Fonti R, Brunetti A, Del Vecchio S. Clin Cancer Res 2014; 2014; 20:4806-4815.
-Reversal of Warburg effect and reactivation of oxidative phosphorylation by differential inhibition of EGFR signaling pathways in non-small cell lung cancer. De Rosa V, Iommelli F, Monti M, Fonti R, Votta G, Stoppelli MP, Del Vecchio S. Clin Cancer Res 2015 (in press).
-Molecular imaging for detection of sensitivity and resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer. Iommelli F, De Rosa V, Fonti R, Del Vecchio S. 2014; 2:43-53. DOI 10.1007/s40336-014-0050-6.
-Sphingosine kinase 1 overexpression contributes to cetuximab resistance in human colorectal cancer models. Rosa R, Marciano R, Malapelle U, Formisano L, Nappi L, D'Amato C, D'Amato V, Damiano V, Marfè G, Del Vecchio S, Zannetti A, Greco A, De Stefano A, Carlomagno C, Veneziani BM, Troncone G, De Placido S, Bianco R. Clin Cancer Res; 2013;1;19(1):138-47.
-Epidermal growth factor receptor activation modulates src-dependent resistance to lapatinib in breast cancer models. Formisano L, Nappi L, Rosa R, Marciano R, D’Amato C, D’Amato V, Damiano V, Raimondo L, Iommelli F, Scorziello A, Troncone G, Veneziani BM, Parsons SJ, De Placido S, Bianco R. Breast Cancer Res; 2014;16(3): R45.
-3'-Deoxy-3'-[18F]-Fluorothymidine PET/CT to guide therapy with epidermal growth factor receptor antagonists and Bcl-xL inhibitors in non-small cell lung cancer. Zannetti A, Iommelli F, Speranza A, Salvatore M, Del Vecchio S. J Nucl Med 2012; 53:443-450.
- PET/CT in cancer research: from preclinical to clinical applications. S. Del Vecchio, A. Zannetti, R. Fonti, F. Iommelli, L. M. Pizzuti, A. Lettieri, M. Salvatore. Contrast Media and Mol Imaging 2010, 5(4):190-200.
-Molecular imaging of tumor microenvironment: challenges and perspectives. Del Vecchio S, Zannetti A, Iommelli F, Lettieri A, Brunetti A, Salvatore M. Q J Nucl Med Mol Imaging, 2010; 54 (3):249-258.
-Molecular imaging of drug resistance in cancer. S. Del Vecchio, A. Zannetti, R. Fonti, F. Iommelli, A. Lettieri, M. Salvatore. Minerva Biotec 2009; 21:31-36.
-Imaging of αvβ3 Expression by a Bifunctional Chimeric RGD Peptide not Cross-Reacting with αvβ5. A. Zannetti, S. Del Vecchio, F. Iommelli, A. Del Gatto, S. De Luca, L. Zaccaro, A. Papaccioli, J. Sommella, M. Panico, A. Speranza, P. Grieco, E. Novellino, M. Saviano, C. Pedone, M. Salvatore Clin. Cancer Res 2009; 15(16): 5224-5233.
-Gefitinib induction of in vivo detectable signals by Bcl-2/Bcl-xL modulation of inositol trisphosphate receptor type 3. A. Zannetti, F. Iommelli, R. Fonti, A. Papaccioli, J. Sommella, A. Lettieri, G. Pirozzi, R. Bianco, G. Tortora, M. Salvatore, S. Del Vecchio. Clin Cancer Res. 2008;14(16):5209-5219.