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Costa, Luís
Lab

Translational Oncobiology

In cancer, metastases are the hallmark of lethality. This unique and complex phenomenon is related not only to the genomic alterations in the cancer cell but also to the heterotypic signalling between cancer cells and host tissues, which could explain metastatic organotropism and how tumours reinvent themselves as new tissues in the target organ. We aim to contribute to the understanding of molecular mechanisms involved in tumour progression at the metastatic site (using bone metastases as paradigm) and to unravel molecular signatures of organotropism by identifying “leader genes signatures” common to primary tumour and the corresponding site of metastases (using Colorectal Cancer (CRC) as model).

  • Research Areas

    • Mechanisms of invasion and progression of solid tumors in bone
    • Mechanisms of invasion and progression of colo-rectal cancer in liver
    • Modulation of sensitivity to antineoplastic agents such as topoisomerase inhibitors
  • Research Team

    • Ongoing Research Projects

      • 2011/2016 Multi-Functional Bone Seeking Agents for the Treatment of Skeletal Metastatic Disease.
      • 2012/2016 Global Cancer Genomics Consorcium.
      • 2013/2016 Luminal-type breast cancer: prognostic value of RANK-positive lymphatic nodes.
      • 2013/2017 Advanced breast cancer: prognosis and therapeutics.
      • 2014/2019 The role of phospholipase C in colorectal cancer
      • 2015/2018 Characterizing the biological role of clinically relevant collagen type I fragments in bone metastatic disease
    • Prizes

      • 2014/2016- Oncology Research Award, Portuguese Foundation Against Cancer / Terry Fox Foundation 

    • Selected Publications

      • Body JJ, Casimiro s, Costa L Targeting bone metastases in prostate cancer: improving clinical outcome. Nature Reviews Urology, 12: 340–356. 2015. doi:10.1038/nrurol.2015.90
      • Ferreira A, Alho I, Casimiro S, Costa L. Bone remodeling markers and bone metastases: From cancer research to clinical implications. Bonekey Rep. 2015 Apr 22;4:668. doi: 10.1038/bonekey.2015.35. eCollection 2015. Review.
      • Costa L. Bisphosphonates in adjuvant setting for breast cancer: a review of the meta-analysis of bisphosphonates' effects on breast cancer recurrence presented in December 2013 at San Antonio Breast Conference. Curr Opin Support Palliat Care. 2014 Dec;8(4):414-9. doi: 10.1097/SPC.0000000000000101. 
      • Casimiro S, Fernandes A, Oliveira AG, Franco M, Pires R, Peres M, Matias M, Tato-Costa J, Guerra N, Ramos M, Cruz J, Costa L. Metadherin expression and lung relapse in patients with colorectal carcinoma. Clin Exp Metastasis. 2014 Aug;31(6):689-96. doi: 10.1007/s10585-014-9659-0. Epub 2014 Jun 20. 
      • Costa L, Casimiro S, Gupta S, Knapp S, Radhakrishna Pillai M, Toi M, Badwe R, Carmo-Fonseca M, and Rakesh Kumar (2014) The global cancer genomics consortium’s third anual symposium: from oncogenomics to cancer care. Genes & Cancer, 5(3-4): 64-70.
      • Fernandes C, Monteiro S, Mendes P, Gano L, Marques F, Casimiro S, Costa L, Correia, JGD, Santos, I Biological assessment of novel bisphosphonate-containing 99mTc/Re-organometallic complexes. Journal of Organometallic Chemistry. 2014 760:197-204.
      • Casimiro S, Alho I, Bettencourt M., Pires R, Lipton A, Costa L RANKL enhances the effect of an antagonist of inhibitor of apoptosis proteins (cIAPs) in RANK-positive breast cancer cells. Journal of Bone Oncology. 2(3): 116-122. 2013
      • Horvath A, Pakala SB, Mudvari P, Reddy SDN, Ohshiro K, Casimiro S, Pires R, 5. Fuqua SAW, Polyak K, Costa L, Toi M, Nair S, Sukumar S, Kumar R Novel Insights into Breast Cancer Genetic Variance through RNA Sequencing. Scientific Reports, 3:2256. 2013 Epub 2013 Jul 25
      • Costa L. Which bisphosphonate to treat bone metastases? Lancet Oncol. 2014 Jan;15(1):15-6. doi: 10.1016/S1470-2045(13)70583-7. Epub 2013 Dec 11. 
      • Alho I, Costa L, Bicho M, Coelho C. Low molecular weight protein tyrosine phosphatase isoforms regulate breast cancer cells migration through a RhoA dependent mechanism. PLoS One. 2013 Sep 27;8(9):e76307. doi: 10.1371/journal.pone.0076307. eCollection 2013.
      • Casimiro S, Mohammad KS, Pires R, Tato-Costa J, Alho I, Teixeira R, Carvalho A, Ribeiro S, Lipton A, Guise TA, Costa L. RANKL/RANK/MMP-1 molecular triad contributes to the metastatic phenotype of breast and prostate cancer cells invitro. PLoS One. 2013 May 16;8(5):e63153. doi: 10.1371/journal.pone.0063153. Print 2013
      • Alho I, Costa L, Bicho M, Coelho C. Characterization of low molecular weight protein tyrosine phosphatase isoforms in human breast cancer epithelial cell lines. Anticancer Res. 2013 May;33(5):1983-7. 
      • Suresh B. Pakala, Suresh K. Rayala, Rui-An Wang, Kazufumi Ohshiro, Prakriti Mudvari, Sirigiri Divijendra Natha Reddy, Yi Zheng, Ricardo Pires, Sandra Casimiro, M. Radhakrishna Pillai, Luis Costa, and Rakesh Kumar MTA1 Promotes STAT3 Transcription and Pulmonary Metastasis in Breast Cancer. Cancer Research, 73(12):3761-3770 2013, Epub 2013 Apr 11.
      • Alho I, Costa L, Bicho M, Coelho C. The role of low-molecular-weight protein tyrosine phosphatase (LMW-PTP ACP1) in oncogenesis. Tumour Biol. 2013 Aug;34(4):1979-89. doi: 10.1007/s13277-013-0784-1. Epub 2013 Apr 14. Review.
      • Fernandes I, Pacheco TR, Costa A, Santos AC, Fernandes AR, Santos M, Oliveira AG, Casimiro S, Quintela A, Fernandes A, Ramos M, Costa L. Prognostic significance of AKT/mTOR signaling in advanced neuroendocrine tumors treated with somatostatin analogs. Onco Targets Ther. 2012;5:409-16. doi: 10.2147/OTT.S36330. Epub 2012 Nov 28. 
      • Global Cancer Genomics Consortium. The Global Cancer Genomics Consortium: interfacing genomics and cancer medicine. Cancer Res. 2012 Aug 1;72(15):3720-4. Epub 2012 May 24. 
      • Clemons M, Russell K, Costa L, Addison CL. Adjuvant bisphosphonate treatment for breast cancer: why did something so elegant become so complicated? Breast Cancer Res Treat. 2012 Jul;134(2):453-7. doi: 10.1007/s10549-012-2077-6. Epub 2012 May 5. Review. 
      • Lipton A, Costa L, Coleman RE. Bone turnover markers: tools for prognosis and monitoring response to bisphosphonates? Breast Dis. 2011;33(2):59-69. doi: 10.3233/BD-2010-0327. 
      • Hadji P, Aapro M, Costa L, Gnant M. Antiresorptive treatment options and bone health in cancer patients-safety profiles and clinical considerations. Cancer Treat Rev. 2012 Oct;38(6):815-24. doi: 10.1016/j.ctrv.2012.03.002. Epub 2012 Apr 5. Review. 
      • Casimiro S, Luis I, Fernandes A, Pires R, Pinto A, Gouveia AG, Francisco AF, Portela J, Correia L, Costa L. Analysis of a bone metastasis gene expression signature in patients with bone metastasis from solid tumors. Clin Exp Metastasis. 2012 Feb;29(2):155-64. doi: 10.1007/s10585-011-9438-0. Epub 2011 Nov 26. 
      • David Henry, Luis Costa, Francois Goldwasser, Vera Hirsh, Vania Hungria, Jana Prausova, Giorgio Vittorio Scagliotti, Harm Sleeboom, Andrew Spencer, Saroj Vadhan-Raj, Roger von Moos, Wolfgang Willenbacher, Penella J Woll, Jianming Wang, Qi Jiang, Susie Jun, Roger Dansey, Howard Yeh.“ A Randomized, Double-blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma” J Clin Oncol (2011), Volume 29, nº 9, pages: 1125-1132
      • Ha NH, Nair VS, Reddy DN, Mudvari P, Ohshiro K, Ghanta KS, Pakala SB, Li DQ, Costa L, Lipton A, Badwe RA, Fuqua S, Wallon M, Prendergast GC, Kumar R.Lactoferrin-endothelin-1 axis contributes to the development and invasiveness of triple-negative breast cancer phenotypes. Cancer Res. 2011 Dec 1;71(23):7259-69. doi: 10.1158/0008-5472.CAN-11-1143. Epub 2011 Oct 17
      • Coleman R, Costa L, Saad F, Cook R, Hadji P, Terpos E, Garnero P, Brown J, Body JJ, Smith M, Lee KA, Major P, Dimopoulos M, Lipton A. Consensus on the utility of bone markers in the malignant bone disease setting. Crit Rev Oncol Hematol. 2011 Dec;80(3):411-32. doi: 10.1016/j.critrevonc.2011.02.005. Epub 2011 Mar 15. Review. 
      • Costa L, Harper P, Coleman RE, Lipton A. Anticancer evidence for zoledronic acid across the cancer continuum. Crit Rev Oncol Hematol. 2011 Feb;77 Suppl 1:S31-7. doi: 10.1016/S1040-8428(11)70006-3. Review.

       

       

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