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web del Instituto de Biología Molecular y Celular

Group name: MOLECULAR AND CELLULAR ONCOLOGY


The main objectives of our research group are, first, the study of the molecular mechanisms associated to chemo and radio resistance in cancer, and second, the search of new therapeutical strategies for the treatment of chemo and radiorresistant tumours, We propose different experimental approaches to raise these objectives:

  1. Development of celular models closer to the patient, allowing ex vivo tests of the treatments.
  2. Development of the several models in order to determine the presence of tumour stem cells in primary cultures.
  3. Use of novel therapies such as epigenetic and enzimatic therapies, in celular models from glioblastoma and pancreatic carcinoma.
  4. Study of signal transduction pathways involved in resistance acquisition in glioblastoma and pancreatic carcinoma. This experimental approach allows the identification of genes involved in this process that can be considered as putative therapeutical targets.

During the last years, nanotechnology development has gained an important boom as a putative therapeutical approach for the treatment of several tumours. The use of immunodirected nanoparticles, will allow:

  • To increase of the local doses and to decrease of the secondary effects.
  • To direct the treatments to celular subpopulations of interest on the tumour, such as tumour stem cells or stroma cells.
  • To combine and direct different and novel therapeutical strategies against the tumours of interest, such as epigenetic and enzimatic therapies.
  • To explore the possibilities of these nanoparticles to potentiate the immunogenic effects observed with classical chemotherapeutical treatments as well as with radiotherapical treatments.

ARTÍCULOS DESTACADOS

BMC Cancer. 2015 Apr 8;15:240. doi: 10.1186/s12885-015-1183-3. HGUE-C-1 is an atypical and novel colon carcinoma cell line. Grasso S, Martínez-Lacaci I, Barberá VM, Castillejo A, Soto JL, Gallego-Plazas J, López-Riquelme N, García-Morales P, Mata-Balaguer T, Ferragut JA, Saceda M

In this article, we have characterize a new cell line of colon carcinoma, obtained from a primary culture fo tumour cells from an ascitic sample of a patient. This novel cell line constitutes a new model of study since it doesn’t show the most frequent mutations observed in colon cancer (KRAS; TP53, BRAF), or microsatellite instability. The resistance profile of this cell line is also very interesting, showing resistance to chemotherapeutical agents used for the treatment of the patient, but, more interestingly, this cell line shows resistance to therapeutical drugs not used for the treatment of the patient, in particular MAPKs pathway inhibitors. The study of the putative resistance mechanisms to these inhibitors in this cell lines, led to the following article.

Neoplasia. 2014 Oct 23;16(10):845-60. doi: 10.1016/j.neo.2014.08.011. eCollection 2014. Resistance to Selumetinib (AZD6244) in colorectal cancer cell lines is mediated by p70S6K and RPS6 activation. Grasso S, Tristante E, Saceda M, Carbonell P, Mayor-López L, Carballo-Santana M, Carrasco-García E, Rocamora-Reverte L, García-Morales P, Carballo F, Ferragut JA, Martínez-Lacaci I.

Once we determine that the cell line HGUE-C-1 was resistant to MAPKs inhibitors and that they showed an increased basal activity of p70S6K, we decided to afford the study of this basal activity as well as the sensitivity and/or resistance to the MAPK inhibitor selumetinib, in a panel of colon carcinoma cell lines and in primary cultures from colon tumours. Our results demonstrated that selumetinib resistance is mediated in these type of tumours, by the activity of p70S6K, and therefore, p70S6K can be considered a molecular marker for sensitivity and/or resistance to selumetinib, as well as a putative therapeutical target against resistance to that pharmacological agent.

SENIOR MEMBERS OF THE RESEARCH GROUP

Miguel Saceda Sánchez

Mª Isabel Martínez-Lacaci Fortuny

Mª Pilar García Morales

PhD STUDENTS

María Fuentes Baile

María Paz Ventero Martin

PUBLICATIONS (ARTICLES)

  1. Transl Oncol. 2014 Oct 24;7(5):590-604. doi: 10.1016/j.tranon.2014.08.001. eCollection 2014. Comparative Study of 17-AAG and NVP-AUY922 in Pancreatic and Colorectal Cancer Cells: Are There Common Determinants of Sensitivity? Mayor-López L1, Tristante E1, Carballo-Santana M1, Carrasco-García E2, Grasso S2, García-Morales P3, Saceda M3, Luján J4, García-Solano J5, Carballo F6, de Torre C1, Martínez-Lacaci I7.
  2. BMC Mol Biol. 2012 Jul 30;13:25. doi: 10.1186/1471-2199-13-25. Dual regulation of P-glycoprotein expression by trichostatin A in cancer cell lines. Balaguer TM1, Gómez-Martínez A, García-Morales P, Lacueva J, Calpena R, Reverte LR, Riquelme NL, Martinez-Lacaci I, Ferragut JA, Saceda M.
  3. Exp Cell Res. 2011 Jun 10;317(10):1476-89. doi: 10.1016/j.yexcr.2011.03.015. Epub 2011 Apr 1. Small tyrosine kinase inhibitors interrupt EGFR signaling by interacting with erbB3 and erbB4 in glioblastoma cell lines. Carrasco-García E1, Saceda M, Grasso S, Rocamora-Reverte L, Conde M, Gómez-Martínez A, García-Morales P, Ferragut JA, Martínez-Lacaci I.
  4. Cancer Lett. 2010 Apr 28;290(2):192-203. doi: 10.1016/j.canlet.2009.09.010. Epub 2009 Nov 5. Selective death of human breast cancer cells by lytic immunoliposomes: Correlation with their HER2 expression level. Barrajón-Catalán E1, Menéndez-Gutiérrez MP, Falco A, Carrato A, Saceda M, Micol V.
  5. Int J Biochem Cell Biol. 2007;39(10):1877-85. Epub 2007 May 21. Protein kinase C-alpha antagonizes apoptosis induction by histone deacetylase inhibitors in multidrug resistant leukaemia cells. Castro-Galache MD1, Menéndez-Gutiérrez MP, Carrasco Garcia E, Garcia-Morales P, Martinez-Lacaci I, Saceda M, Ferragut JA.
  6. Mol Cancer Res. 2007 Jun;5(6):641-53. Post-transcriptional regulation of P-glycoprotein expression in cancer cell lines. Gómez-Martínez A1, García-Morales P, Carrato A, Castro-Galache MD, Soto JL, Carrasco-García E, García-Bautista M, Guaraz P, Ferragut JA, Saceda M.
  7. Oncogene. 2007 Nov 8;26(51):7185-93. Epub 2007 May 21. Inhibition of Hsp90 function by ansamycins causes downregulation of cdc2 and cdc25c and G(2)/M arrest in glioblastoma cell lines. García-Morales P1, Carrasco-García E, Ruiz-Rico P, Martínez-Mira R, Menéndez-Gutiérrez MP, Ferragut JA, Saceda M, Martínez-Lacaci I.
  8. Mol Cancer Ther. 2006 Sep;5(9):2172-81. Cyclin D3 is down-regulated by rapamycin in HER-2-overexpressing breast cancer cells. García-Morales P1, Hernando E, Carrasco-García E, Menéndez-Gutierrez MP, Saceda M, Martínez-Lacaci I.
  9. Mol Cancer Ther. 2005 Aug;4(8):1222-30. Histone deacetylase inhibitors induced caspase-independent apoptosis in human pancreatic adenocarcinoma cell lines. García-Morales P1, Gómez-Martínez A, Carrato A, Martínez-Lacaci I, Barberá VM, Soto JL, Carrasco-García E, Menéndez-Gutierrez MP, Castro-Galache MD, Ferragut JA, Saceda M.
  10. J Endocrinol. 2004 Mar;180(3):497-504. Regulation of estrogen receptor-alpha expression by the tumor suppressor gene p53 in MCF-7 cells. Angeloni SV1, Martin MB, Garcia-Morales P, Castro-Galache MD, Ferragut JA, Saceda M.