grupo

Group name: Liquid biopsy and metastasis

    Group leader
  • Jose Antonio Lorente
  • Senior Researcher
  • Pedro Sánchez Rovira
  • M. Jose Serrano Fernández
  • Jose Luis García Puche
  • Juan Carlos Álvarez Merino

Presentation Video

SCIENTIFIC INTEREST AREAS

Biological implications of CTCs in the metastatic process: Control of growth and tumor dormancy

The systemic nature of breast cancer is defined by the dissemination of early tumor cells, even with relatively small tumors. In this scenario, the metastatic process may involve the dissemination of circulating tumor cells (CTCs) through the blood and lymphatic system prior to the colonization of distant organs. Several studies have regarded CTCs in peripheral blood as the pre-stadium of clinically manifest distant metastases. Furthermore, recent evidence have validated the prognostic capacity of CTCs, and highlighted the importance of CTCs analyses in those patients without clinical evidence of metastasis.
As a result of acquired chemoresistance, an increasing number of patients experience disease progression following first-line chemotherapy. In this context, the prognostic role of CTCs might prove critical in efforts to predict risk of further metastases and in the therapeutic decision process

RESEARCH AREAS

  • Investigation line 1: Genetic characterization of circulating tumor cells (CTCs) and the primary tumor in breast cancer patients: identification of new prognostic markers. In recent years, the perspective of the study of breast cancer has changed considerably, and the importance local curative treatment has declined in favour of the administration of chemotherapy treatments or even in the absence of lymph node and small tumor size. The identification of new prognostic factors that allow us to discriminate and stratify patients for individualized treatment is one of the most important avenues of research in this field. Among these new markers, the presence of circulating tumor cells (CTCs) is considered indicative of hematogenous spread factor with considerable potential prognostic significance in metastasis formation. Recent studies show that these cells may have stem cell characteristics, which seem to play a crucial role in the initiation and progression of cancer as well as the ability to be resistant to chemotherapy treatments. The aim of this study is to determine the prognostic value of the presence of these cells in peripheral blood of breast cancer patients without metastasis, genetic and phenotypic characterization, in addition to the primary tumor arising. This allows us to include patients with primary breast cancer within subgroups that require more intensive clinical monitoring.
  • Investigation line 2: Molecular mechanisms of tumor dormancy in breast cancer. The evidence suggests that microscopic dormant tumors are not only common but also highly prevalent in healthy individuals. Due to its small size and non-invasive nature, these dormant tumors are asymptomatic and, in many cases without being detected. With advances in diagnostic imaging and molecular biology is becoming increasingly clear that such tumors may remain asymptomatic stage, to stand for an extended period of time without increasing in size. Elucidate the mechanisms regulating these processes will be instrumental in identifying new biomarkers of early cancer and may serve as a basis for the development of therapies based on tumor biology of this process. Despite the high prevalence of microscopic tumors, latent in the human and the important clinical implications of early detection, this area of cancer research, has to date, few studies.
  • Investigation line 3: Markers of response to treatment in lung cancer The standard treatment of non-small cell lung cancer has undergone a dramatic change with the introduction of genetic data of expression of molecules involved in carcinogenesis. So now, cancer patients with advanced non-small cell lung, that overexpress EGFR mutation of T790, should be treated with inhibitors as TIK Genfitinib or Erlotinib, rather than the standard QT schemes. This has opened a new avenue for treating this serious disease and poor survival prognosis, advanced stages. However, despite the benefits of the treatments described, there are a certain percentage of patients still present these mutations not respond to treatment with inhibitors of tyrosine kinase
  • Investigation line 4: Angiogenic and structural marker related to sudden death. The most common cause of sudden death (MS) is of cardiac origin (MSC) (90%) and within this, myocardial ischemia is the most frequent (75%). The cessation of blood flow to the heart muscle leads to a series of structural changes, biochemical and molecular, but when a man suddenly dies as a result of ischemia / myocardial infarction, not enough time for structural changes evident, making it difficult to diagnose the cause of death. Our goal is to make an early diagnosis of ischemic MSC through molecular markers. In our study, we analyze molecules as potential molecular markers of myocardial ischemic pain, with the purpose of knowing the early molecular response to myocardial ischemia. This research helps to establish the precise diagnosis of the cause and mechanism of sudden death ischemic heart, allowing to provide data on the intensity, duration and extent of myocardial ischemia. On the other hand, allow us to determine the kinetics and pattern of release of these markers with the consequent possibility of earlier detection following the introduction of cardiac ischemia.
  • Investigation line 5: Functional genomics in the development of new therapeutic strategies against breast cancer. During the latest decades, the development of new diagnostic and surgical technologies and the design of new therapeutic agents have positively impacted breast cancer treatment. Nevertheless, nowadays patients with equal diagnosis and prognosis can show different response to treatment and divergent clinical outcomes, what evidence the high degree of heterogeneity of this disease and the limits of our current knowledge about the molecular mechanisms that direct the therapeutic response of breast cancer patients. High throughput techniques lately employed in transcriptomics and proteomics, have been shown to be useful tools to study key molecular processes in oncogenesis and tumor progression, as well as for the identification of the molecular pathways that interact to lead chemoresistant phenotypes. Our research line is focused on this latest issue and includes experimental designs towards the identification of genes whose expression is modified by chemotherapy and the molecular pathways in which they participate. The main objective of this approach is the development of new biological therapies able to disrupt the survival and adaptive capacities of highly chemoresistant and clinically aggressive breast tumors

TECHNOLOGY PLATFORMS

  • Plataforma 1:Confocal Microscopy
  • Plataforma : Laser Microdissection: PALM Microbeam
  • AFFIMETRIX: CGH
  • ABI 7900 real time
  • ABI 7500 real time
  • Cytometry

FUNDING

  • INSTITUTO CARLOS III FIS por colaboración con Hospital del MAR (Barcelona)
  • CEIFA.
  • Consejeria de Economia Innovación y Ciencia. CTS 5350

SELECTED PUBLICATIONS

MJ Serrano, JA Lorente, JC Álvarez, I Martínez, A. Fernández, PS Rovira. Clinical relevance associated to the analysis of circulating tumor cells in patients with solid tumors. Clinical and Transl Oncol 10: 659-668 (2009).

Gaforio JJ, Serrano MJ, Sanchez-Rovira P, Sirvent A, Delgado-Rodriguez M, Campos M, de la Torre N, Algarra I, Duenas R, Lozano A.Detection of breast cancer cells in the peripheral blood is positively correlated with estrogen-receptor status and predicts for poor prognosis.Int J Cancer. Dec 20;107(6):984-90.( 2003)

Maria José Serrano, P Sánchez-Rovira, M. Delgado-Rodríguez and J.J. Gaforio. Detection of circulating tumor cells in the context of treatment.Cancer Biology & Therapy. (2009).

Maria Jose Serrano; Jose Antonio Lorente Acosta; Miguel Delgado Rodriguez; Ana Fernández; Mónica Fernández; Capilla de la Torre; Jaime Fernández, Pedro Sánchez Rovira.Circulating tumor cells in peripheral blood: potential impact in breast cancer outcome Clinical and Translational Oncology (2011).

Laura Vera Ramírez; Pedro Sanchez Rovira; Cesar Ramirez Tortosa; Jose Luis Quiles Morales; Maria Carmen Ramirez Tortosa; Juan C. Alvarez ; Monica Maria Fernandez Navarro; José Antonio Lorente Acosta;Gene-expression profiles, tumor microenvironment, and cancer stem cells in breast cancer.latest advances towards an integrated approach high-activity variants of the umaoa polymorphism increase the risk for depression in a large primary. Cancer Treatment reviews, issn: 0305-7372. (2010).

Vera-Ramirez L, Sanchez-Rovira P, Ramirez-Tortosa MC, Ramirez-Tortosa CL, Granados-Principal S, Lorente JA, Quiles JL. Free radicals in breast carcinogénesis, breast cancer progresión and cancer ítem cells. Biological bases to develop oxidative-based therapies.Crit Rev Oncol Hematol. (2011).

LORENTE M, Lorente JA, WILSON MR, BUDOWLE B, VILLANUEVA E. Sequential multiplex amplification (SMA) of genetic loci: a method for recovering template DNA for subsequent analyses of additional loci. International Journal of Legal Medicine, 107: 156-158 (1994).

Sweet DJ, Lorente M, Valenzuela A, Lorente JA, Alvarez JC. Increasing DNA extraction yield from saliva stains with a modified Chelex method. Forensic Science International 83: 167-177.(1996).

Vera-Ramirez L, Sanchez-Rovira P, Ramirez-Tortosa CL, Quiles JL, Ramirez Tortosa MC, Alvarez JC, Fernandez-Navarro M, Lorente JA.Gene expresión profiles, tumor microenviorement, and cancer ítem cells in breast cancer: lastet advances towards an integrated approach. Cancer Treat Rev. 2010 Oct;36(6):477-84. ( 2010)

Sánchez-Muñoz A, García-Tapiador AM, Dueñas-García R, Jaén-Morago A, Ortega-Granados AL, Martínez-Ortega E, Fernández Morales M, Fernández-Navarro M, de la Torre Cabrera C, Dueñas B, Ureña C, Martínez J, Morales F, Ramírez-Tortosa C, Sánchez-Rovira P.Safety and efficacy of neo-adjuvant sequential dose-dense chemotherapy doublets combined with trastuzumab in patients with HER-2-positive early stage breast cancer. Breast J. 2008;14(5):506-7.(2008)