Studies on thoracic cancers (mesothelioma and lung cancer)

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

1. 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.
   Link: www.ncbi.nlm.nih.gov/pubmed/25483224
2. 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
   Link: www.ncbi.nlm.nih.gov/pubmed/24953979
3. 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
   Link: www.ncbi.nlm.nih.gov/pubmed/24803580
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
   Link: www.ncbi.nlm.nih.gov/pubmed/24167634
5. 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
   Link: www.ncbi.nlm.nih.gov/pubmed/24041630
6. 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
   Link: www.ncbi.nlm.nih.gov/pubmed/24138720
7. 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
   Link: www.ncbi.nlm.nih.gov/pubmed/23857408
8. 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
   Link: www.ncbi.nlm.nih.gov/pubmed/23456625
9. 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
   Link: www.ncbi.nlm.nih.gov/pubmed/22978339
10. 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
    Link: www.ncbi.nlm.nih.gov/pubmed/22894673
11. 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
    Link: www.ncbi.nlm.nih.gov/pubmed/21970874
    Free pdf: click here
12. 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
    Link: www.ncbi.nlm.nih.gov/pubmed/21652582
13. 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
    Link: www.ncbi.nlm.nih.gov/pubmed/21262916
14. 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
    Link: www.ncbi.nlm.nih.gov/pubmed/21332310
15. 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
    Link: www.ncbi.nlm.nih.gov/pubmed/21196162
16. 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
    Link: www.ncbi.nlm.nih.gov/pubmed/20351322
17. 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
    Link: www.ncbi.nlm.nih.gov/pubmed/20159991
18. 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
    Link: www.ncbi.nlm.nih.gov/pubmed/19292993
19. 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
    Link: www.ncbi.nlm.nih.gov/pubmed/19102717
20. 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
    Link: www.ncbi.nlm.nih.gov/pubmed/18347182
21. 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
    Link: www.ncbi.nlm.nih.gov/pubmed/18187583