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«CURRICULUM VITAE Name: Luis António Marques da Costa Date of Birth: June 8, 1961. S.Paulo. Brazil Present Title and Affiliation: Director of the ...»

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Name: Luis António Marques da Costa

Date of Birth: June 8, 1961.

S.Paulo. Brazil

Present Title and Affiliation:

Director of the Oncology Division at Hospital de Santa Maria

Professor of Medicine & Biology of Cancer – Faculdade de Medicina de Lisboa

Principal Investigator of Instituto de Medicina Molecular (IMM) – Research Leader of

The Clinical Translational Oncology Research Unit at IMM.

Director of Clinical Research Center at CAML-Centro Académico de Medicina de Lisboa.

Office Address:

Serviço de Oncologia do Hospital de Santa Maria Piso 3 1649-035 Lisboa tel: + 217805096 Fax: + 217805615 Email: luis.costa@hsm.min-saude.pt luiscosta.oncology@gmail.com Research Theme/ Focus My interests in clinical research have been focus in the area of bone metastases since

1995. The clinical projects were designed and developed in Lisbon (Hospital de Santa Maria) in collaboration with the Penn State University (Dr. Allan Lipton research team).

We tested the clinical value of type I bone collagen fragments to monitor treatment response in patients with bone metastases. The results achieved were published and have been used as biochemical parameters of response in clinical trials testing new drugs to treat bone metastases.

The interpretation of some of the results observed in our previous research lead us to disclose the role of matrix metalloproteinases (MMPs) in osteoclast independent mechanisms of bone degradation. Since then we pursue the hypothesis that MMPs, namely MMP1 have a central role in bone metastases progression and resistance to bisphosphonates. The purpose of this research is to identify biochemical pathway-based molecular targets and develop agents to intervene phenotypic cancer signaling in metastatic setting.

More recently, we became also interested in testing the role of collagen fragments derived from MMP1 activity over collagen type as growth/survival factors for cancer cells. In 2008 our Translational Research Unit was selected twice to receive the Therry Fox award. These basic research projects have been developed at IMM.

We are evaluating in a clinical trial the synergism interaction between bisphosphonates and taxanes in breast cancer and prostate cancer with bone metastases.

Over the years, we have been collaborating with Dr. Rakesh Kumar former chairman of Department of Molecular & Cellular Oncology UT M. D. Anderson Cancer Center, Houston, Texas in research projects involving human breast tumor samples from our institution. As an example we identified a correlation between the presence of lymph node metastases and the expression of paxillin in tumor samples. Our collaboration at the present is focus on Triple Negative Breast Cancer and in genomics of synchronous bilateral cancer, as part of the Global Cancer Genomics Consortium activities.

In the Oncology Division at Hospital de Santa Maria I have been collaborating as principal investigator of several international clinical trials (phase 2 and 3) testing the therapeutic effectiveness of new agents. Our division is active at the moment in 20 international clinical studies. In the last two years I have been acting as principal investigator in 12 clinical trials in breast cancer, as well as principal investigator of clinical trials testing new drugs for bone metastases (breast cancer; prostate cancer; other solid tumors).

Our Research Unit at Instituto de Medicina Molecular is now developing new projects to understand the relationship between estrogen dependence and cancer cell tropism to bone; and to determine the role of phospholipase C epsilon in Colon Cancer progression.


–  –  –

Academic Appointments:

Assistant Professor of Medicine, Faculdade de Medicina de Lisboa, University of Lisbon 1995-2002 PhD in Medical Oncology (Thesis on Bone Metastases) 2002 Professor of Medicine, Faculdade de Medicina de Lisboa, University of Lisbon Principal Investigator of the Molecular Medicine Institute 2002 (IMM) University of Lisbon Visiting Professor at the M.D. Anderson Cancer Center 2003, 2004 Head of the Clinical Translational Oncology Research Unit 2007-present (CTORU) at IMM

–  –  –

Coordinator Professor of “Oncobiologia” – Teaching Unit at school of Medicine Faculdade de Medicina de Lisboa 2009-present


Certified Portuguese Board of Internal Medicine Certified Portuguese Board of Medical Oncology Certified member of ESMO (European Society of Medical Oncology)

Medical and Scientific Societies:

Portuguese Board of Internal Medicine Portuguese Board of Medical Oncology American Society of Medical Oncology European Society of Medical Oncology European Association for Cancer Research ASPIC, Associação Portuguesa de Investigação em Cancro.

Member of the Direction Committee of the Portuguese Society of Oncology (2003-5) Portuguese representative of the Global Cancer Genomics Consortium Member of the Scientific Program Committee for 12th International Conference on Cancer-Induced Bone Disease (Lyon, 2012).

Research support:

Principal Investigator, Prognostic Signatures in Colorectal Cancer (PSCC).

FCT: PIC/IC/82821/2007 FLAD: support to PhD in Oncology – 2002.

Principal Investigator, Analysis of RANK/RANKL and MMPs in clinical samples of solid tumors bone metastases – 2008-2010, Amgen, inc, USA – Multi-Functional Bone Seeking Agents for the Treatment of Skeletal Metastatic Disease. Coordinator: Luis Costa. FCT, PTDC/QUI-QUI/115712/2009,


Reviewer of Scientific Manuscripts

Annals of Oncology; Bone; British Journal of Cancer; Critical Reviews in Oncology/Hematology; Cancer Letters; European Journal of Cancer; Breast Cancer Research and Treatment; The Oncologist; Cancer Treatment Reviews;

Therapeutic Advances in Medical Oncology; The Breast; Lancet Oncology;

Drugs; Lancet.

Member of the Editorial board of Harvard Medical School Portugal Program Member of the Editorial Board - Journal of Bone Oncology (JBO) Member of the Editorial Board – Plos One Expert Reviewer of Grants European Research Council Cancer Research UK Member of CAIBER Evaluators Panel (Spanish Clinical Research Network) French National Cancer Institute Committee of INSERM unit evaluation

Main publications:

Biochemical markers of bone turnover in patients with metastatic bone disease.

Laurence M.Demers, Luis Costa, Vernon Chinchilli, Allan Lipton.

Clinical Chemistry, vol.41 nº10:1489-1494, 1995.

Effect of Fadrozole Hydrochloride (CGS 16949) on cholesterol,lipid, and hemostatic parameters in women with advanced breast cancer.

L.Costa, M.Kopreski, V.Chinchilli, R.Santen, H.Harvey, A.Lipton.

Cancer 85(1) 100-103, 1999.

Markers of Bone Resorption in Patients Treated with Pamidronate.

A.Lipton, L.Demers, E.Curley, V.Chinchilli, L.Gaydos, G.Hortobagyi, R.Theriault, D.Clemens, L.Costa et al.

European Journal of Cancer vol.33, nº13, 2021-2026, 1998.

Transcriptional Up-Regulation of Paxillin Expression by Heregulin in Human Breast Cancer Cells.

R. Vadlamudi, L.Adam, B.Tseng, L.Costa, R.Kumar.

Cancer Research 59 (12): 2843-2846, June 15, 1999.

Biochemical markers and Skeletal metastases.

Laurence Demers, Luis Costa, Allan Lipton.

Cancer suppl. Vol. 88: 2919-2926, June 15, 2000.

Bone markers in the management of metastatic bone disease.

A.Lipton, L.Costa, S.M.Ali and L.M.Demers.

Cancer Treatment Reviews, suppl. 1-5, 2001 Growth Factors regulate heterogeneous Nuclear Ribonucleoprotein K expression and Function.

Manitosh Mandal, Ratna Vadlamudi, Diep Nguyen, Rui-An Wang, Luis Costa, Rozita Bagheri-Yarmand, John Mendelson and Rakesh Kumar.

Journal of Biological Chemistry vol.276, nº13:9699-9704, 2001.

Safety and efficacy of bisphosphonates beyond 24 months in cancer patients.

S.M.Ali, F.J.Esteva, G.Hortobagyi, H.Harvey, J.Seaman, R.Knight, L.Costa, A.Lipton.

Journal of Clinical Oncology vol. 19, nº14: 3434-3437, 2001.

Use of markers of bone turnover for monitoring bone metastases and the response to therapy.

Allan Lipton, Luis Costa, Suhail Ali, Laurence Demers.

Seminars in Oncology vol.28, nº4, suppl 11: 54-59, 2001.

Prospective evaluation of the peptide-bound collagen type I cross-links Ntelopeptide and C-telopeptide in predicting bone metastases status.

Luis Costa, Laurence M.Demers, A.Gouveia-Oliveira, J.Schaller, Eduardo B.Costa, Miguel C.Moura, Allan Lipton.

Journal of Clinical Oncology, vol. 20: 850-856, 2002.

Biochemical Markers and Skeletal Metastases Laurence Demers, Luis Costa, Allan Lipton Clinical Orthopaedics and Related Research, nº 415S, pp 1-10, 2003.

Baseline serum NTx Levels are Prognostic in Metastatic Breast Cancer Patients with Bone-only Metastasis S.M.Ali, L.M.Demers, K.Leitzel, H.A.Harvey, D.Clemens, N.Mallinack, L.Engle, V.Chinchilli, L.Costa, C.Brady, J.Seaman & A.Lipton.

Annals of Oncology 15: 455- 459, 2004 “Role of Bisphosphonates for the Management of Skeletal Complications and Bone Pain from Skeletal Metastases” Luis Costa; Allan Lipton and Robert Coleman Supportive Cancer Therapy vol. 3, nº 3: 143-153, 2006 “Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel” M. Aapro, P. A. Abrahamsson, J. J. Body, R. E. Coleman, R. Colomer, L. Costa, L. Crino`, L. Dirix, M. Gnant, J. Gralow, P. Hadji, G. N. Hortobagyi, W. Jonat, A.

Lipton, A. Monnier, A. H. G. Paterson, R. Rizzoli, F. Saad & B. Thurlimann.

Annals of Oncology 19(3):420-432, 2008 “Bisphosphonates: Reducing the risk of skeletal complications from bone metastasis” L.Costa Breast Dec; 16 suppl 3: S16-20; 2007 “Low molecular weight protein tyrosine phosphatase genetic polymorphism and susceptibility for cancer development” Irina Alho, Maria Clara Bicho, Raquel Carvalho, Alda Pereira da Silva, Luís Costa, Manuel Bicho.

Cancer Genetics and Cytogenetics 181 (2008): 20-24 “Clinical Characteristics and Therapeutic Options in Paget Disease of The Breast” Isabel Fernandes, João Borges da Costa, Luis Soares de Almeida, Maria Pires de Miranda, Luis Costa, Marques Gomes.

Skin cancer. Vol 22, nº2 June 2007: 65-68 “Impact of Skeletal Complications on Patients' Quality of Life, Mobility, and Functional Independence” Luis Costa, Xavier Badia; Edward Chow; Allan Lipton; Andrew Wardley Supportive Care in Cancer (2008): 16: 879-889 “Effect of Bisphosphonates on Pain and Quality of Life in Patients With Bone Metastases” Luis Costa and Pierre P Major.

Nature Clinical Practice Oncology (2009) vol.

6, nº 3: 163-174 “99mTc-Tricarbonyl Complexes Functionalized 1 with Anthracenyl Fragments:

Synthesis, Characterization and Evaluation of Their Radiotoxic Effects in Murine Melanoma Cells Rute F. Vitor, Teresa Esteves, Fernanda Marques, Paula Raposinho, Antonio Paulo, Sebastiao Rodrigues, Jose Rueff, Sandra Casimiro, Luis Costa and Isabel Santos.

Cancer Biotherapy & Radiopharmaceuticals (2009) “Phase I Trial of Zoledronic Acid + Imatinib Mesylate (Gleevec) in Patients With Bone Metastases” Lipton A, Campbell Baird C, Harvey H, Kim C, Demers L, Costa L.

Am J Clin Oncol. (2010) Feb; 33(1):75-8.

“Prognostic Factors for Skeletal Complications From Metastatic Bone Disease in Breast Cancer” Janet E. Brown, MD; Richard J Cook; Allan Lipton; Luis Costa; Robert E Coleman Breast Cancer Res Treat (2010) 123:767–779 Zoledronic Acid: Its Use in the Treatment of Breast Cancer.

Luis I, Casimiro S, Ribeiro J and Costa L Clinical Medicine Insights: Therapeutics (2010) 2, 903-926.

“Optimizing Clinical Benefits of Bisphosphonates in Cancer Patients With Bone Metastases” Matti Aapro, Fred Saad, Luis Costa The Oncologist (2010): Volume 15, Issue #11, pages 1147-1158 “ 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” 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.

J Clin Oncol (2011), Volume 29, nº 9, pages: 1125-1132 “ Anticancer evidence for zoledronic acid across the cancer continuum” Luis Costa, Peter Harper, Robert Coleman, Allan Lipton Critical Reviews in Oncology/Hematology 2011 Feb; 77 Suppl 1:S31-7. Review “Consensus on the Utility of Bone Markers in the Malignant Bone Disease Setting”.

R. Coleman; L. Costa; et al Critical Reviews in Oncology/Hematology (2011) Dec;80 (3):411-32. Epub 2011 Mar 15 “Lactoferrin- Endothelin-1 Axis Contributes to the Development and Invasiveness of Triple Negative Breast Cancer Phenotypes” Ngoc-Han Ha, Vasudha Nair, Divijendra Natha Sirigiri Reddy, Prakriti Mudvari, Kazufumi Ohshiro, Krishna Sumanth Ghanta, Suresh B. Pakala, Da-Qiang Li, Luis Costa, Allan Lipton, Rajendra A. Badwe, Suzanne Fuqua, Margaretha Wallon, George C.Prendergast, and Rakesh Kumar Cancer Res. 2011 Dec 1;71(23):7259-7269. Epub 2011 Oct 17 “Analysis of a bone metastasis gene expression signature in patients with bone metastasis from solid tumors” Casimiro S, Luis I, Fernandes A, Pires R, Pinto A, Gouveia AG, Francisco AF, Portela J, Correia L, Costa L.

Clin Exp Metastasis. 2012 Feb;29(2):155-64. doi: 10.1007/s10585-011-9438-0.

Epub 2011 Nov 26 “Bone Turnover markers: Tools for prognosis and monitoring response to bisphosphonates” Lipton A, Costa L, Coleman RE.

Breast Dis. 2011 Jan 1;33(2):59-69.

“Hospital Resource Utilization and Treatment Cost of Skeletal-Related Events in Patients with Metastatic Breast or Prostate Cancer: Estimation for the Portuguese National Health System” J. Félix, V. Andreozzi, M. Soares, P. Borrego, H. Gervásio, A. Moreira, L. Costa, F. Marcelo, F. Peralta, I. Furtado, F. Pina, C. Albuquerque, A. Santos, J.L. Passos-Coelho, for the Portuguese Group for the Study of Bone Metastases VALUE IN HEALTH 1 4 ( 2011) 499 – 505 “Castration-resistant Prostate Cancer: Mechanisms, Targets and Treatment”.

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