New targeted anticancer agents

During the last decade novel anticancer treatments have emerged from advances in understanding of tumor biology, and a number of molecular targets have been identified. New drugs have been developed to attack these targets. They are used to neutralize specific molecules or genes involved in cancer development (“targeted therapy”). To date, only a few of these agents can offer hope of a substantial impact on the natural history of the disease.

One of the reasons for the relative failure of the first generation of clinical trials of targeted therapy could be the multilevel cross-stimulation among the targets of the new biological agents along several pathways of signal transduction involved in neoplastic events. Blocking only one of these pathways allows others to act as salvage mechanisms for cancer cells. Therefore, the study of key biomarkers and combinations of biological compounds with both chemotherapy and other targeting compounds is an essential issue in the novel treatment modalities against cancer.

Our main articles related to this project

1. Van Zweeden AA, van der Vliet HJ, Wilmink JW, Meijerink MR, Meijer OW, Bruynzeel AM, van Tienhoven G, Giovannetti E, Kazemier G, Jacobs MA, Verheul HM.
   Phase I clinical trial to determine the feasibility and maximum tolerated dose of panitumumab to standard gemcitabine-based chemoradiation in locally advanced pancreatic cancer.
   Clin Cancer Res. 2015 Jun 8. pii: clincanres.3364.2014. [Epub ahead of print] Link: www.ncbi.nlm.nih.gov/pubmed/26056353
2. Galvani E, Sun J, Leon LG, Sciarrillo R, Narayan RS, Tjin Tham Sjin R, Lee K, Ohashi K, Heideman DA, Alfieri RR, Heynen GJ, Bernards R, Smit EF, Pao W, Peters GJ, Giovannetti E.
   NF-κB drives acquired resistance to a novel mutant-selective EGFR inhibitor.
   Oncotarget. 2015 Apr 29. [Epub ahead of print] Link: www.ncbi.nlm.nih.gov/pubmed/26015408
   Free pdf: click here
3. Porcelli L, Giovannetti E, Assaraf YG, Jansen G, Scheffer GL, Kathman I, Azzariti A, Paradiso A, Peters GJ.
   The EGFR pathway regulates BCRP expression in NSCLC cells: role of erlotinib.
   Curr Drug Targets. 2014;15(14):1322-30.
   Link: www.ncbi.nlm.nih.gov/pubmed/25479544
4. Giovannetti E, Leon LG.
   New strategies and applications for drugs targeting EGFR and c-Met
   J Cancer. 2015 Jul;51(11):1389-404.
   Link: www.ncbi.nlm.nih.gov/pubmed/25382191
5. Maftouh M, Avan A, Sciarrillo R, Granchi C, Leon LG, Rani R, Funel N, Smid K, Honeywell R, Boggi U, Minutolo F, Peters GJ, Giovannetti E.
   Synergistic interaction of novel lactate dehydrogenase inhibitors with gemcitabine against pancreatic cancer cells in hypoxia
   Br J Cancer. 2014 Jan 7;110(1):172-82.
   Link: www.ncbi.nlm.nih.gov/pubmed/24178759
6. Avan A, Caretti V, Funel N, Galvani E, Maftouh M, Honeywell RJ, Lagerweij T, Van Tellingen O, Campani D, Fuchs D, Verheul HM, Schuurhuis GJ, Boggi U, Peters GJ, Würdinger T, Giovannetti E.
   Crizotinib inhibits metabolic inactivation of gemcitabine in c-Met-driven pancreatic carcinoma
   Cancer Res. 2013 Nov 15;73(22):6745-56.
   Link: www.ncbi.nlm.nih.gov/pubmed/24085787
7. Avan A, Maftouh M, Funel N, Ghayour-Mobarhan M, Boggi U, Peters GJ, Giovannetti E.
   MET as a potential target for the treatment of upper gastrointestinal cancers: characterization of novel c-Met inhibitors from bench to bedside
   Curr Med Chem. 2014;21(8):975-89.
   Link: www.ncbi.nlm.nih.gov/pubmed/23992325
8. García-Santisteban I, Peters GJ, Giovannetti E, Rodríguez JA.
   USP1 deubiquitinase: cellular functions, regulatory mechanisms and emerging potential as target in cancer therapy
   Mol Cancer. 2013 Aug 10;12:91.
   Link: www.ncbi.nlm.nih.gov/pubmed/23937906
9. Galvani E, Giovannetti E, Saccani F, Cavazzoni A, Leon LG, Dekker H, Alfieri R, Carmi C, Mor M, Ardizzoni A, Petronini PG, Peters GJ.
   Molecular mechanisms underlying the antitumor activity of 3-aminopropanamide irreversible inhibitors of the epidermal growth factor receptor in non-small cell lung cancer
   Neoplasia. 2013 Jan;15(1):61-72.
   Link: www.ncbi.nlm.nih.gov/pubmed/23359111
   Free pdf: click here
10. Giovannetti E, Labots M, Dekker H, Galvani E, Lind JS, Sciarrillo R, Honeywell R, Smit EF, Verheul HM, Peters GJ.
    Molecular mechanisms and modulation of key pathways underlying the synergistic interaction of sorafenib with erlotinib in non-small-cell-lung cancer (NSCLC) cells
    Curr Pharm Des. 2013;19(5):927-39.
    Link: www.ncbi.nlm.nih.gov/pubmed/22973961
11. Avan A, Crea F, Paolicchi E, Funel N, Galvani E, Marquez VE, Honeywell RJ, Danesi R, Peters GJ, Giovannetti E.
    Molecular mechanisms involved in the synergistic interaction of the EZH2 inhibitor 3-deazaneplanocin A with gemcitabine in pancreatic cancer cells
    Mol Cancer Ther. 2012 Aug;11(8):1735-46.
    Link: www.ncbi.nlm.nih.gov/pubmed/22622284
    Free pdf: click here

For our ongoing studies on drug resistance and new models to test targeted antitumor agents we obtained a CCA Foundation grant. This was reported in the leaflet of the Foundation, distributed during the Amsterdam Marathon 2012
See: CCA leaflet