The Translational Medical Oncology Laboratory, led by Miguel Abal (I3SNS researcher at IDIS-SERGAS), is dedicated to the study of the process of metastasis as the most relevant clinical event in oncology, and focusing mainly on the colonization of circulating tumor cells (CTC) and the formation of distal metastases. From the characterization of CTCs to the remodeling of distal niches for the reception of prone metastatic cells, we aim to better understand the molecular and cellular mechanisms that regulate these events and to develop strategies to impair tumor dissemination and metastatic colonization.
The Translational Medical Oncology Laboratory
Based on clear unmet clinical needs, we design and develop research projects to provide solutions that can be translated into clinical practice. The M-Trap technology developed by the group represents an example of this approach: a medical device designed to capture disseminating tumor cells and to control peritoneal metastasis through the focalisation of the disease (de la Fuente et al., J Natl Cancer Inst. 2015; 107 (9):djv184; Alonso-Alconada et al., Dis Model Mech. 2020; 13(6):dmm043653). Based on positive preclinical results and regulatory analysis, we have obtained the authorisation from AEMPS to conduct a proof of conceptclinical trial in patients with advanced ovarian cancer (NCT03085238). Similarly, the research on communication between tumor cells and the environment and the transfer of information through extracellular vesicles (exosomes), resulted in the development of ExoGAG, a new technology for the efficient purification of EVs from clinical samples with demonstrated clinical value in liquid biopsy (Herrrero et al., Cancers (Basel) 2019; 11(12):2000).
In addition to developing clinical solutions against the process of metastasis, the group in specially interested in the translational research in endometrial cancer. This line of research involves the ginecologists (Ana Vilar, Efigenia Arias, Victoria Sampayo) and oncologists (Juan Cueva) from our hospital, together with the Liquid Biopsy Unit (Laura Muinelo) at IDIS. We approach the characterization of CTCs isolated from patients with advanced endometrial cancer (Alonso-Alconada et al., Mol Cancer. 2014; 13: 223; Carcinogenesis. 2014; 35 (12): 2679-86; Int J Cancer. 2015; 136 (8): 1863-73), the characterization and impact of VEs on the efficiency of the process of dissemination of CTCs and metastatic colonization (Mariscal et al., J Proteome Res. 2019; 18 (3): 1043 -1053), and the clinical value of the combination of uterine aspirate and plasma ctDNA as forms of liquid biopsy in endometrial cancer patients with high risk of recurrence (Casas-Arozamena et al., J Clin Med. 2020; 9 (2): 585). This line of research is funded by ISCIII (PI17/01919) and AECC (Coordinated Clinical Groups 2018), and the group actively participates in the national (www.geicen.com) and European (https://www.esgo.org/network/enitec/) in endometrial cancer, as well as in the development of clinical practice guidelines (Colombo et al., ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up. Ann Oncol . 2016; 27 (1): 16-41).
Finally, the group is interested in the generation of new preclinical models that more reliably reproduce the clinical events associated with the process of metastasis. On the one hand, we participate in the development of dynamic 3D co-culture systems based on microfluidics, for the isolation and monitoring of CTC (Nieto et al., Coloides Surf B Biointerfaces 2015; 134: 363-9), for the study of the interaction between CTC and metastatic niches (Otero-Cacho et al., Sci Rep. 2018; 8: 2795), and for new treatments through high-throughput-screening. On the other hand, we developed in vivo systems based on organoids and preclinical models in zebrafish (Cabezas-sainz et al., BMC Cancer. 2018; 18: 3) and in mice (PDX, patient-derived xenografts; Casas-Arozamena et al., J Clin Med. 2020; 9 (2): 585), to facilitate the transfer of our results to the clinic.