Perfil metabolómico de los tumores neuroendocrinos de origen gastrointestinal y pulmonar : papel pronóstico y relevancia biológica

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 11-02-2022Reprogrammed metabolism encompasses the capacity of cells to respond or adapt their metabolic signalling to support and enable cell survival in unfavourable or hostile conditions. This ability is enhanced in cancer cells to improve their adaptive phenotype and maintain both viability and uncontrolled proliferation. Metabolic flexibility is therefore one of the key hallmarks of cancer, although pathways involved in the metabolic plasticity of each cancer type remain to be elucidated. Metabolites are the final products of this adaptation, reflecting the aberrant changes in the genomic, transcriptomic and proteomic variability of tumors, and therefore provide useful biological and clinical information on cancer biology. This, together with the fact that metabolomics can be easily performed in readily accessible biological samples (i.e. plasma, urine), makes metabolic profiling of cancer patients a promising tool to characterize the tumor phenotype and identify novel biomarkers of potential clinical use...La reprogramación del metabolismo permite a las células para responder o adaptar su regulación metabólica para permitir la supervivencia celular en condiciones desfavorables u hostiles. Esta capacidad aumenta en las células cancerosas para mejorar su fenotipo adaptativo y mantener tanto la viabilidad como la proliferación incontrolada. Así, la flexibilidad metabólica es una de las características distintivas del cáncer, aunque todavía quedan por dilucidar las vías implicadas en la plasticidad metabólica de cada tipo de tumor. Los metabolitos son los productos finales de esta adaptación, que en último término reflejan los cambios aberrantes que sufren los tumores reflejando la variabilidad genómica, transcriptómica y proteómica de los mismos y, por lo tanto, proporcionando información relevante sobre la biología del cáncer. Además, el estudio de los perfiles de metabolitos (metabolómica) puede realizarse fácilmente en muestras biológicas de fácil acceso (plasma, orina), constituyendo así una herramienta prometedora para caracterizar el fenotipo tumoral e identificar nuevos biomarcadores de potencial utilidad clínica...Fac. de MedicinaTRUEunpu

The Role and Expression of Angiogenesis-Related miRNAs in Gastric Cancer

Gastric cancer (GC) is the fifth most frequently diagnosed malignant tumor and the third highest cause of cancer mortality worldwide. For advanced GC, many novel drugs and combinations have been tested, but results are still disappointing, and the disease is incurable in the majority of cases. In this regard, it is critical to investigate the molecular mechanisms underlying GC development. Angiogenesis is one of the hallmarks of cancer with a fundamental role in GC growth and progression. Ramucirumab, a monoclonal antibody that binds to vascular endothelial growth factor-2 (VEGFR-2), is approved in the treatment of advanced and pretreated GC. However, no predictive biomarkers for ramucirumab have been identified so far. Micro RNAs (miRNAs) are a class of evolutionarily-conserved single-stranded non-coding RNAs that play an important role (via post-transcriptional regulation) in essentially all biologic processes, such as cell proliferation, differentiation, apoptosis, survival, invasion, and migration. In our review, we aimed to analyze the available data on the role of angiogenesis-related miRNAs in GC

Capecitabine plus temozolomide in well- or moderately-differentiated primary atypical neuroendocrine tumours — single-centre experience of two cases

Introduction: Neuroendocrine neoplasms (NENs) are a rare and heterogeneous group of tumours, with a variety of primary origins and variable aggressiveness. NENs with an atypical primary origin, such as breast and retroperitoneal NENs, are extremely rare. As a consequence, an established diagnostic and therapeutic strategy in this particular subgroup is lacking. The combination of capecitabine and temozolomide, called CAPTEM regimen, has produced promising response rates in patients with grade 1 or 2 neuroendocrine tumours of multiple origins. Case presentation: The first is a case of a 68-year-old woman with a metastatic primary breast neuroendocrine tumour, treated with cisplatin plus etoposide as first line, followed by CAV scheme (cyclophosphamide, doxorubicin, and vincristine), and subsequently treated, in third line with the CAPTEM regimen, obtaining radiological response and good tolerance. The second is the case of a 66-year-old woman affected by a metastatic primitive retroperitoneal NET G2. The patient progressed after a somatostatin analogue-based first line, whereas the CAPTEM regimen led to a partial and durable response with a favourable safety profile. Conclusions: CAPTEM chemotherapy has been shown to be an active and safe therapeutic option in advanced, metastatic G1/2 atypical primary NENs

Somatostatin Analogue Therapy in MEN1-Related Pancreatic Neuroendocrine Tumors from Evidence to Clinical Practice: A Systematic Review

Neuroendocrine neoplasms (NENs) are relatively rare and complex tumors that can be sporadic or hereditary, as in the context of multiple endocrine neoplasia type 1 (MEN1) where patients display a 70% lifelong risk of developing a pancreatic NENs (pNENs). To date, specific personalized treatment for pNENs in patients with MEN1 are lacking. The aim of this study was to systematically analyze the efficacy and safety of somatostatin analogue (SSA) treatment in patients affected by MEN1-related pNENs. We performed a systematic review of the literature, searching for peer-reviewed articles on SSA (octreotide or lanreotide) treatment in MEN1 associated with pNENs. We selected 20 studies with a pooled population of 105 MEN1 patients with pNENs. Females were 58.5%, median age was 44 years (18–73). TNM stage at diagnosis was stage I–II in 84.8% and stage IV in 15.2%. The overall response rate (SD+PR+CR) was achieved in 88.3% of cases, with stable disease in 75.6% and objective response in 12.7% of patients. The safety profile was favorable with both SSA agents. SSAs appear to be an effective and safe treatment option for MEN1-related pNEN, either at localized or advanced stages.Depto. de MedicinaFac. de MedicinaTRUEMinisterio de Ciencia e Innovación (España)pu

Cell-based medicinal products approved in the European Union: current evidence and perspectives

Advanced Therapy Medicinal Products (ATMPs) are innovative clinical treatments exploiting the pharmacological, immunological, or metabolic properties of cells and/or gene(s) with the aim to restore, correct, or modify a biological function in the recipient. ATMPs are heterogeneous medicinal products, developed mainly as individualized and patient-specific treatments, and represent new opportunities for diseases characterized by a high-unmet medical need, including rare, genetic and neurodegenerative disorders, haematological malignancies, cancer, autoimmune, inflammatory and orthopaedic conditions. Into the European Union (EU) market, the first ATMP has been launched in 2009 and, to date, a total of 24 ATMPs have been approved. This review aims at reporting on current evidence of cell-based therapies authorized in the EU, including Somatic Cell Therapies, Tissue Engineering Products, and Cell-based Gene Therapy Products as Chimeric Antigen Receptor (CAR) T-cells, focusing on the evaluation of efficacy and safety in clinical trials and real-world settings. Despite cell-based therapy representing a substantial promise for patients with very limited treatment options, some limitations for its widespread use in the clinical setting remain, including restricted indications, highly complex manufacturing processes, elevated production costs, the lability of cellular products over time, and the potential safety concerns related to the intrinsic characteristics of living cells, including the risk of severe or life-threatening toxicities, such as CAR-T induced neurotoxicity and cytokine release syndrome (CRS). Although encouraging findings support the clinical use of ATMPs, additional data, comparative studies with a long-term follow-up, and wider real-world evidences are needed to provide further insights into their efficacy and safety profiles