Our research program on Thoracic Cancers is a multifaceted effort designed to understand thoracic cancer biology, discover novel agents and improve treatment.
For our ongoing studies on mesothelioma we recently obtained a grant from the Mesothelioma Applied Research Foundation (US)
See: Press Release
Novel agents hold also great promise for lung cancer patients. A key development in cancer research over the past year is understanding how to rationally target the right treatments for the right patient in order to improve outcomes for all. We have therefore studied the biology of the epidermal growth factor receptor (EGFR) and how mutations (and polymorphisms) play a key role in explaining the uniquely strong responses seen when administering EGFR tyrosine kinase inhibitors to certain lung cancer patients. Now we are actively examining strategies to overcome both intrinsic and acquired resistance to anti-EGFR therapy.
Another major focus of our research effort has been pharmacogenetics of lung cancer. Similar to our studies with EGFR, the ultimate goal of this work is facilitating more rationale treatment selections for patients. Our group has also made key observations regarding the role of cytidine deaminase and outcome from cancer therapy. Clinical trials further examining this relationship are underway.
Our main articles related to this project
- Leon LG, Gemelli M, Sciarrillo R, Avan A, Funel N, Giovannetti E.
Synergistic activity of the c-Met and tubulin inhibitor tivantinib (ARQ197) with pemetrexed in mesothelioma cells
Curr Drug Targets. 2014;15(14):1331-40.
- Rolfo C, Giovannetti E, Hong DS, Bivona T, Raez LE, Bronte G, Buffoni L, Reguart N, Santos ES, Germonpre P, Taron M, Passiglia F, Van Meerbeeck JP, Russo A, Peeters M, Gil-Bazo I, Pauwels P, Rosell R.
Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors
Cancer Treat Rev. 2014 Sep;40(8):990-1004
- Avan A, Maftouh M, Avan A, Tibaldi C, Zucali PA, Giovannetti E.
SNPs in PI3K-PTEN-mTOR and brain metastases in NSCLC–letter
Clin Cancer Res. 2014 Jul 1;20(13):3623-4
- La Monica S, Caffarra C, Saccani F, Galvani E, Galetti M, Fumarola C, Bonelli M, Cavazzoni A, Cretella D, Sirangelo R, Gatti R, Tiseo M, Ardizzoni A, Giovannetti E, Petronini PG, Alfieri RR.
Gefitinib inhibits invasive phenotype and epithelial-mesenchymal transition in drug-resistant NSCLC cells with MET amplification
PLoS One. 2013 Oct 22;8(10):e78656
- Bronte G, Rolfo C, Giovannetti E, Cicero G, Pauwels P, Passiglia F, Castiglia M, Rizzo S, Vullo FL, Fiorentino E, Van Meerbeeck J, Russo A.
Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment? Biological, pharmacological and clinical aspects
Crit Rev Oncol Hematol. 2014 Feb;89(2):300-13
- 5- Galvani E, Toffalorio F, Peters GJ, De Pas T, Giovannetti E.
Pharmacogenetics of non-small cell lung cancer (NSCLC): time to “work it out”?
Curr Pharm Des. 2014;20(24):3863-74
- Giovannetti E, Peters GJ, Zucali PA.
“One marker does not fit all”: additional translational and validation studies are needed to identify faithful predictors of pemetrexed activity in mesothelioma
J Thorac Oncol. 2013 Aug;8(8):e79-80
- Azijli K, Yuvaraj S, van Roosmalen I, Flach K, Giovannetti E, Peters GJ, de Jong S, Kruyt FA.
MAPK p38 and JNK have opposing activities on TRAIL-induced apoptosis activation in NSCLC H460 cells that involves RIP1 and caspase-8 and is mediated by Mcl-1
Apoptosis. 2013 Jul;18(7):851-60
- Erdem L, Giovannetti E, Leon LG, Honeywell R, Peters GJ.
Polymorphisms to predict outcome to the tyrosine kinase inhibitors gefitinib, erlotinib, sorafenib and sunitinib
Curr Top Med Chem. 2012;12(15):1649-59
- Galvani E, Peters GJ, Giovannetti E.
EGF receptor-targeted therapy in non-small-cell lung cancer: role of germline polymorphisms in outcome and toxicity
Future Oncol. 2012 Aug;8(8):1015-29
- Giovannetti E, Zucali PA, Assaraf YG, Leon LG, Smid K, Alecci C, Giancola F, Destro A, Gianoncelli L, Lorenzi E, Roncalli M, Santoro A, Peters GJ.
Preclinical emergence of vandetanib as a potent antitumour agent in mesothelioma: molecular mechanisms underlying its synergistic interaction with pemetrexed and carboplatin
Br J Cancer. 2011 Nov 8;105(10):1542-53
Free pdf: click here
- Tibaldi C, Giovannetti E, Tiseo M, Leon LG, D’Incecco A, Loosekoot N, Bartolotti M, Honeywell R, Cappuzzo F, Ardizzoni A, Peters GJ.
Correlation of cytidine deaminase polymorphisms and activity with clinical outcome in gemcitabine-/platinum-treated advanced non-small-cell lung cancer patients
Ann Oncol. 2012 Mar;23(3):670-7
- Zucali PA, Giovannetti E, Destro A, Mencoboni M, Ceresoli GL, Gianoncelli L, Lorenzi E, De Vincenzo F, Simonelli M, Perrino M, Bruzzone A, Thunnissen E, Tunesi G, Giordano L, Roncalli M, Peters GJ, Santoro A.
Thymidylate synthase and excision repair cross-complementing group-1 as predictors of responsiveness in mesothelioma patients treated with pemetrexed/carboplatin
Clin Cancer Res. 2011 Apr 15;17(8):2581-90
- Lemos C, Giovannetti E, Zucali PA, Assaraf YG, Scheffer GL, van der Straaten T, D’Incecco A, Falcone A, Guchelaar HJ, Danesi R, Santoro A, Giaccone G, Tibaldi C, Peters GJ.
Impact of ABCG2 polymorphisms on the clinical outcome and toxicity of gefitinib in non-small-cell lung cancer patients
Pharmacogenomics. 2011 Feb;12(2):159-70
- Giovannetti E, Erdem L, Olcay E, Leon LG, Peters GJ.
Influence of polymorphisms on EGFR targeted therapy in non-small-cell lung cancer
Front Biosci (Landmark Ed). 2011 Jan 1;16:116-30
- Giovannetti E, Tibaldi C, Falcone A, Danesi R, Peters GJ.
Impact of cytidine deaminase polymorphisms on toxicity after gemcitabine: the question is still ongoing
J Clin Oncol. 2010 May 10;28(14):e221-2
- Giovannetti E, Zucali PA, Peters GJ, Cortesi F, D’Incecco A, Smit EF, Falcone A, Burgers JA, Santoro A, Danesi R, Giaccone G, Tibaldi C.
Association of polymorphisms in AKT1 and EGFR with clinical outcome and toxicity in non-small cell lung cancer patients treated with gefitinib
Mol Cancer Ther. 2010 Mar;9(3):581-93
- Danesi R, Pasqualetti G, Giovannetti E, Crea F, Altavilla G, Del Tacca M, Rosell R.
Pharmacogenomics in non-small-cell lung cancer chemotherapy
Adv Drug Deliv Rev. 2009 May 20;61(5):408-17
- Danesi R, Altavilla G, Giovannetti E, Rosell R.
Pharmacogenomics of gemcitabine in non-small-cell lung cancer and other solid tumors
Pharmacogenomics. 2009 Jan;10(1):69-80
- Tibaldi C, Giovannetti E, Vasile E, Mey V, Laan AC, Nannizzi S, Di Marsico R, Antonuzzo A, Orlandini C, Ricciardi S, Del Tacca M, Peters GJ, Falcone A, Danesi R.
Correlation of CDA, ERCC1, and XPD polymorphisms with response and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients
Clin Cancer Res. 2008 Mar 15;14(6):1797-803
- Giovannetti E, Lemos C, Tekle C, Smid K, Nannizzi S, Rodriguez JA, Ricciardi S, Danesi R, Giaccone G, Peters GJ.
Molecular mechanisms underlying the synergistic interaction of erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, with the multitargeted antifolate pemetrexed in non-small-cell lung cancer cells
Mol Pharmacol. 2008 Apr;73(4):1290-300