Medicina individualizada en tumores sólidos

RESEARCH INTEREST

The Research Group «Individualized Medicine in Solid Tumors» of the IIS-La Princesa (https://www.iis-princesa.org/grupo/grupo-40/) is integrated into the area «Advanced Therapies and Individualized Medicine» coordinated by Dr. Manuel Ramírez Orellana, as part of the accredited Health Research Institute (IIS-Princesa). Group 40 is located at the University Hospital of La Princesa (Madrid), a high-complexity hospital, and a reference center in the Community of Madrid for different surgical specialties and subspecialties, which has its own Ministry of Health-endorsed Biomedical Research Foundation, providing an advanced healthcare and research environment for translational research and clinical studies. It also includes research members from the Hospital Universitario Santa Cristina.

Group 40 has a consolidated track record and sustained competitive activity, oriented towards precision oncology, biomarkers and precision surgery, and with proven experience in the training and motivation of clinical-researcher profiles including predoctoral students, Rio Hortega and Juan Rodés contracts. The research group is associated with the UAM Chair of Personalized Precision Medicine (UAM- Instituto Roche) (https://www.institutoroche.es/catedra_de_medicina_personalizada_de_precision), directed by Dr. Ramon Colomer (Medical Oncology) and Dr. Sánchez Madrid (Immunology).

Group 40 focuses on clinical and translational research with the aim of identifying, validating and implementing biomarkers and precision therapeutic strategies in patients with solid tumours that optimise clinical decision-making and improve health outcomes, coinciding with one of the priority lines of research of the AES 2026 call. The results of our group have an impact on the optimization of public resources, reducing side effects and increasing the probabilities of clinical benefit of the available strategies. Its work model is based on multidisciplinary hospital collaboration and stable external collaborations with national and international groups such as CNIO and EORTC.

The scientific group is led by Dr. Ramon Colomer and by Dr. Nuria Romero-Laorden as co-leader, guaranteeing scientific supervision and training support in translational and clinical research aimed at implementable results. Dr. Nuria Romero-Laorden joined the management of the group after a Juan Rodés contract (JR17/00007). The group’s capacity is based on access to clinical cohorts and biological samples, experience in the design and execution of studies with a translational component, and institutional support for translational research and clinical trials. In recent years, the group has demonstrated its continued ability to attract competitive funding and to execute projects aimed at biomarkers in precision oncology, adding 6 projects granted by ISCIII since 2018: PI17/01865, PI17/00801, PI20/01458, PI21/01111, PMP22/00032 and PI25/01173.

The following is a summary of the current lines of research:

1. Biomarkers in precision oncology: discovery, validation and implementation.
The group is developing a priority line focused on biomarkers with clinical applicability in precision oncology, aimed at patient stratification, response prediction and the identification of resistance mechanisms. The approach is translational, from discovery to validation in clinical cohorts and its possible implementation in care, and has been consolidated with competitive funding from the ISCIII. This is the context of PIE15/00068 («Discovery, Validation and Implementation of Biomarkers for Precision Oncology»), a coordinated and multicentre platform promoted by oncologists and pathologists to improve the coordination of professionals involved in oncological biomarkers, integrating five hospitals (12 de Octubre, Ramón y Cajal, Valdecilla, IRB Lleida and La Princesa) and two collaborating centres (Vall d’Hebron and the Institute of Biomedicine of Seville).

In addition, the group has contributed to the conceptual standardization of the clinical use of NGS with guidance publications for its indication, including rare tumors (Colomer R, Miranda J, Romero-Laorden N, et al., EClinicalMedicine, 2023). The incorporation of Nuria Romero-Laorden brought previous experience in a multicenter platform of biomarkers in prostate cancer with more than 900 patients in which 56 hospitals have participated, having achieved high-impact publications with FWCI>6 (PMIDs: 37838555, 30773204, 38417742, 40467032) in collaboration with CNIO and international researchers from the IRCSS in Italy, University College London, the University of Washington or British Columbia University in Canada. Finally, this line is reinforced with the promotion of emerging researchers betting on the transmission of leadership with the project co-led by Jacobo Rogado together with Ramon Colomer (PI25/01173), focused on biomarkers of efficacy/toxicity of immunotherapy in non-small cell lung cancer, with preliminary results on immune trafficking/chemotaxis in peripheral blood and its relationship with body composition and leptin for prospective validation.

2. Actionable molecular alterations and therapeutic stratification in solid tumors. Line aimed at the identification and characterization of molecular alterations with therapeutic relevance in solid tumors, evaluating their usefulness as actionable biomarkers and their correlation with clinical phenotypes and response to treatment. This included the project «Double amplification with therapeutic relevance in hormone-dependent breast cancer» (PI17/01865).
Dr. Romero-Laorden developed a Phase 2 trial as a PI to analyze the benefit of switching prednisone to dexamethasone in prostate cancer patients treated with abiraterone (SWITCH; Br J Cancer 2018), identifying a new therapeutic strategy that has been recognized and included in International Clinical Guidelines (NCCN guidelines 2021 DOI: 10.6004/jnccn.2021.0008), occupying the publication an outstanding 84th percentile of citations in its area and showing our ability to obtain results with a direct impact on care in the NHS.

This line is supported by the close connection with the hospital’s Clinical Trials Unit, which provides a stable research structure and contributes to the sustainability of the group. In addition, activity in clinical trials facilitates continuous contact with new drugs and therapeutic strategies, and allows molecular information to be transferred more quickly to stratification and treatment selection decisions.

3. Immunological biomarkers and immunophenotypic profile in advanced cancer.
Translational line aimed at the study of immunological determinants associated with therapeutic response, resistance or escape in advanced cancer, with the aim of identifying transferable biomarkers and supporting precision medicine strategies. As an example, the group has developed the project «Immunophenotype in metastatic prostate cancer» (PI21/01111), which reflects the group’s ability to carry out immune biomarker studies in a highly complex clinical context.
Also, Dr. Jacobo Rogado has focused on biomarkers of efficacy and toxicity of immunotherapy, especially in non-small cell lung cancer, with more than 50 articles since 2018 (20 as first author or corresponding author) and a notable impact (more than 1200 citations since 2020 and more than 1300 accumulated; PMIDs: 30682533, 32363123, 35740564, 35870091, 29910159, 39708256). His work integrates clinical biomarkers and host variables (including immunorelated adverse events; PMID 30682533, and excess weight; PMIDs 32363123 and 35870091) with a translational approach based on immunophenotyping in peripheral blood. This line is prospectively validated in project PI25/01173.

The execution is supported by the stable collaboration with Immunology (Dr. Alfranca and Dr. Sánchez-Madrid), the support of IIS-Princesa platforms (flow cytometry, PCR and traceable sample circuit) and both national and international collaborations (EORTC-LCG, EORTC-H&N, GECP, TTCC). In addition, it is reinforced with competitive funding led by Dr. Nuria Romero-Laorden: AECC project in melanoma (PRYCO223002PEIN), Mutua Madrileña MUT02.2021 and projects in metastatic prostate cancer (PI17/00801; PI21/01111; CRIS Foundation Clinical Talent Program Against Cancer 2022).

4. Metabolic determinants and their connection with tumor processes (with translational projection).
Translational line aimed at exploring relevant metabolic processes in cancer and their application both in prevention and in the identification of useful biological determinants for individualized medicine. This is the framework of the project «A new metabolic strategy for the prevention of breast cancer» (PI14/00726), which exemplified the group’s approach to metabolic targets with preventive potential.
In a complementary way, the line studies tumor lipid metabolism and its connection with the immune microenvironment, analyzing determinants linked to FASN and its relationship with the T cell compartment in the tumor, with interest in biomarkers and response/resistance mechanisms. This strand is structured around the project «A novel tumorigenic role of Fatty Acid Synthase related to the tumor T-cell compartment» (PI20/01458). The execution of this line is reinforced by stable external collaborations, including CNIO, which provide a complementary framework for the development and testing of hypotheses in tumour biology.

5. Clinical research in hepatobiliopancreatic surgery.
The Hepatobiliopancreatic Surgery Unit of the University Hospital of La Princesa is a clinical group made up of hepatobiliopancreatic surgeons, medical and radiation oncologists, radiologists, interventional radiologists, gastroenterologists, and pathologists who work together in a multidisciplinary way in the diagnosis and treatment of patients with hepatobiliopancreatic pathology.

The unit’s goal is to provide personalized cancer treatment, offering the best treatment available to each of our patients. We have extensive experience in the diagnostic and therapeutic approach to pancreatic pathology, such as pancreatic cancer, neuroendocrine tumors and cystic lesions, among others, as well as in the management of primary and metastatic benign and malignant liver lesions. Since the incorporation of the Da Vinci robot, research has focused on the minimally invasive/precision treatment of these pathologies to demonstrate their clinical and oncological benefits. In addition, we have presented a large number of communications to national and international conferences and publications, as well as participation in clinical research projects in collaboration with other groups.

The group’s main areas of research are:

• Surgical treatment of pancreatic carcinoma and its complications.
• Robotic approach to hepatobiliopancreatic pathology.
• Identification of prognostic and predictive factors of response to chemotherapy treatment.
• Impact of exocrine pancreatic insufficiency in subjects with pancreatic cancer.
• Evaluation of quality of life in patients undergoing surgery for pancreatic cancer.

Within the participation in clinical trials, the collaborative projects with other centers granted by ISCIII stand out:
PI19/00250: Pancreatic anastomosis after cephalic duodenopancreatectomy: Pancreatogastrostomy verses Blumgart’s anastomosis. Multicenter, prospective, randomized study.
PI16/01465: Impact of the spread of circulating tumor cells during cephalic duodenopancreatectomy in patients with pancreatic and periampullary tumors on the development of distant metastases and survival. Prospective, randomized, multicenter study.
PI15/00076: Cephalic duodenopancreatectomy in pancreatic and periampullary tumors: initial approach to the superior mesenteric artery versus the classic approach. Prospective, randomized, multicenter study
PI20/00047: Survival Analysis of Neoadjuvant Treatment in Resectable Pancreatic Carcinoma with Risk Factors
PI01/0264: Study and characterization of molecules involved in progression to metastatic phenotype. Assessment of its diagnostic potential and therapeutic use.
PI09/1336: Anti-tumor therapeutic potential of anti-CCR7 antibodies.

6. Study of biomarkers in cytological and tissue samples of small size.
This a practical issue is of special importance given the necessarily small size of many samples (tissue and cytological) resulting from minimally invasive diagnostic procedures, which aim to reduce the possible morbidity for the patient. This problem applies to the anatomopathological diagnosis of practically all neoplasms, with special relevance, due to its frequency and inaccessibility, to lung and pancreatic cancer. In this context, the diagnostic use of fine needle aspiration (FNA) (transbronchial and echoendoscopic) has multiplied in recent years. Their small size requires their rational use, as well as the extrapolation of molecular immunohistochemical techniques to cytological material. The study of this type of sample is the subject of preferential analysis in the Pathological Anatomy Service of the La Princesa University Hospital. Since 2012, numerous cytological studies have been published with special interest in the application of immunohistochemistry to this type of samples. As a result of this research, the Service is currently participating in the drafting of three of the monographic texts of the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO) dedicated to diagnostic cytopathology, and proposed as diagnostic references for international use.

7. Clinical research in gynaecological and breast cancer
The Gynaecological Oncology and Breast Cancer mixed Unit of the HU Santa Cristina-HU La Princesa is a multidisciplinary and inter-hospital unit made up of gynaecologists, medical oncologists, radiation oncologists, radiologists and pathologists, who work together in the diagnosis and treatment of patients with gynaecological and breast cancer.

The aim of the unit is to treat gynaecological and breast cancer in a personalised way. We have extensive experience in both surgical and systemic diagnostic and therapeutic approaches, including all available lines of treatment. In breast surgery, advanced oncoplastic surgery, risk-reducing surgeries and non-excisional treatments such as thermoablation or cryotherapy are performed. For the surgical treatment of gynecologic cancer, both minimally invasive approaches and maximum-effort debulking surgeries are performed for advanced ovarian cancer and gynecologic cancer recurrences.

The group’s research focuses on clinical results of treatments, research work is regularly presented in the form of communications at national and international conferences and scientific publications, it also actively participates in clinical research projects in collaboration with other groups.

The group’s main areas of research are:

• Anatomopathological results of different oncoplasty patterns in breast cancer.
• Surgical de-escalation in breast cancer patients treated with neoadjuvant therapy.
• Identification of prognostic and predictive factors of complete cytoreduction in advanced ovarian cancer.
• Evaluation of quality of life in patients undergoing surgery for gynecologic cancer.